Cardiovascular Research, 1975, 9,47-55.
Changes in regional coronary blood flow with hypertonic mannitol in conscious dogs’ I A N HUTTON, SAMUEL P . MARYNICK, D A V I D E. FIXLER, G O R D O N H . T E M P L E T O N , and J A M E S T . W I L L E R S O N
From the Pauline and Adolph Weinberger Laboratory for Cardiopulmonary Research of the Department of Internal Medicine, the Department of Pediatrics, and the Department of Physiology, Uniiiersity of Texas Southwestern Medical School at Dallas, Dallas, Texas, USA
Systemic haemodynamics and regional myocardial blood flow responses to hypertonic mannitol were studied in 10 conscious and 23 anaesthetized dogs. Mannitol infusion significantly increased regional myocardial blood flow in the conscious, intact dogs. Mannitol increased total coronary flow 20% in anaesthetized animals compared to 80% in the awake ones. In both groups mannitol exerted a significant positive inotropic effect as evidenced by increases in maximal LV dp/dt and dp/dt/p. These studies have also demonstrated that the intact conscious dog that has not received any sedation has an inner:outer wall left ventricular flow ratio greater than 1.0. AUTHORS’ SYNOPSIS
This study was supported by NHLI contract 72-2947. by NHLI research grant HL 15522, and by grants from the American Heart Association, Inc and the American Heart Association, Texas Affiliate, Inc. This work was performed during Dr Hutton’s tenure as a BritishAmerican Research Fellow of the American Heart Association and British Heart Foundation. His present address is: Department of Medical Cardiology, Royal Infirmary, Glasgow. Dr Willerson is an established investigator of the American Heart Association. 1
physiologically intact animals following hypertonic mannitol. In view of the potential clinical application of hypertonic mannitol, it was decided to assess its effects on both total and regional myocardial blood flow and ventricular function in conscious, intact dogs. This study presents an extension of previous observations in a more physiological preparation and provides new information regarding flow changes in the myocardium. In addition, the opportunity was taken to make certain comparisons between awake and anaesthetized dogs of the influence of hypertonic mannitol on myocardial function and coronary blood flow.
Materials and methods Ten adult mongrel dogs weighing 12-20 kg were anaesthetized with sodium pentobarbital (30mg/kg), intubated, and ventilated with a Harvard respirator using a gas mixture of 95% O2 and 5% C 0 2 .Sterile thoracotomies were performed through a left lateral incision. A calibrated solid-state pressure transducer (Konigsberg P21) with a frequency
Downloaded from by guest on June 6, 2016
It has been previously demonstrated that hypertonic agents exert a positive inotropic effect in both the anaesthetized dog (Wildenthal et al, 1969a) and in the isolated cat papillary muscle (Koch-Weser, 1963; Wildenthal et al, 1969b). Hypertonic mannitol has been reported to improve ventricular function and reduce myocardial damage while increasing total coronary blood flow during acute myocardial ischaemia in anaesthetized dogs (Willerson et al, 1972). Using isolated perfused canine hearts and a krypton washout technique, increases in collateral coronary blood flow have also been reported following hypertonic mannitol during acute myocardial ischaemia (Willerson et al, 1972). There have been no previous measurements of regional myocardial blood flow in
48 Hutton, Marynick, Fixler, Templeton, and Willerson
+
a small Holter pump with each microsphere injection. At the conclusion of the study the heart was removed, cut into right and left ventricles and ventricular septum, and each region subsequently dissected into inner or subendocardial, middle, and outer or subepicardial regions. The different regions of the heart and the reference blood samples were placed into separate scintillation vials and counted in a well scintillation detector (Nuclear Chicago). Regional myocardial blood flow was determined from the equation: myocardial flow myocardial nuclide activity reference sample flow . reference sample nuclide activity The radioactivity emitted from each nuclide was determined by the method of Rudolph and Heymann (1967) modified by using the reference sample technique to calculate flows and using different calibration constants for differential spectrometry. Arterial blood samples were taken at regular intervals for blood gas determination (Instrumentation Laboratories model 31 3), haematocrit (International Company microhaematocrit), and osmolality measurement (Fisk osmometer freezing point determination)l. The contractile state of the heart was assessed by determining the maximal rate of left ventricular pressure rise (dp/dt max) and the quotient of dp/dt and developed left ventricular pressure (dp/dt/p) during isovolumic contractions (Mason et a/, 1971). The dogs were trained to lie unsedated in a cradle and the study was not commenced unless the heart rate was less than 130 per minute. Each animal was atrially paced at a rate of 10-20 beats above his own heart rate. After initial measurements, either isotonic saline or dextrose was infused into the superior vena cava using a Harvard constant infusion pump at a rate of 7.6 ml./min for 20 min and then 3.8 ml./min for an additional 10 min. Pressures were continuously monitored. Cardiac output and myocardial blood flow were measured at the end of each infusion. The animal was allowed to recover over a 1 hr period and 25% mannitol was then infused into the superior vena cava at the previous rates of infusion. When the osmolality and haemodynamics had returned to the original steady state measurement, an average of 2+ hr after the administration of mannitol, either isotonic saline o r dextrose was infused again. In the anaesthetic studies, 23 adult mongrel dogs anaesthetized with chloralose (60 mg/kg) were similarly studied ; total coronary blood flow was measured from a 12 G polyvinyl catheter placed in 1
Range of error i 3 mom.
Downloaded from by guest on June 6, 2016
response greater than 1,000 Hz was introduced into the left ventricle through a stab incision near the apex. Pacing electrodes were sutured on both the left atrial appendage and on the right ventricle. A 15-gauge polyvinyl catheter was placed within the left atrial appendage. The pericardium was usually loosely resutured and the catheters and pacing wires were exteriorized at the back of the neck. The dogs were allowed 2-3 weeks to recover before being again anaesthetized with sodium pentobarbital and having 15-gauge polyvinyl catheters introduced into the superior vena cava and the thoracic aorta via the external carotid artery. All catheters were kept patent by intermittent flushing with heparin. Haemodynamic and coronary blood flow studies were performed 24 to 48 hr after insertion of the arterial and venous catheters. At the time of the study, left atrial and systemic arterial pressures were measured using Statham P23Db transducers and recorded on an Electronics for Medicine recorder. The zero reference point for both pressures was taken as midthorax with the dog lying in a cradle. The left ventricular end-diastolic pressure obtained from the solid-state transducer was adjusted so that it was equal to the mean left atrial pressure obtained from the internal left atrial catheter. The P21 Konigsberg transducer has a temperature error of 0.05 mm Hg/”C; there were no significant shifts in the stability of the Konigsberg transducer over the length of the acute experiments reported in this study. The left ventricular pressure was continuously differentiated using an R C differentiator to provide the rate of rise of pressure in the left ventricle, LV dp/dt. A cardiotachometer triggered by the electrical signal from the pressure pulse provided a precise measurement of heart rate which was kept constant by atrial pacing using a Grass S4 stimulator. Cardiac output was measured by the dye-dilution technique using indocyanine green dye as the indicator. The green dye was injected into the superior vena cava and blood withdrawn at a constant rate from the thoracic aorta through a densitometer and the dilution curve recorded (Lyons Medical Corporation). All outputs were done in duplicate and the mean of the results taken. The electrocardiogram was monitored continuously. Total and regional myocardial blood flows were measured using a radioisotope technique (Domenech ef d, 1969; Buckberg et a/, 1971). Microspheres, 8 ,u in diameter, labelled with 46Sc,*?3r, and 141Ceand lZ5l microspheres (15 IL in diameter) suspended in saline were used to measure the regional myocardial blood flow by alternately injecting a different microsphere into the left atrium. A reference blood flow sample was collected from the carotid artery in 30-sec fractions over a 2-min period using
49 Mannitol and total and regional myocardial blood flow
the coronary sinus and stabilized with suture ligation. Hypertonic mannitol (25%) or isotonic saline was administered intravenously at 3.81 ml./ min for 30 min. Regional myocardial blood flows were not measured in the studies on anaesthetized animals. The distal end of the coronary sinus catheter communicated with the left femoral vein and a 3-way stopcock allowed coronary sinus flow to be measured directly. Heart rate was kept constant by atrial pacing. Left ventricular, systemic arterial pressure, and LV dp/dt were measured. Statistical comparisons in all of the studies were made using the t test for paired data.
TABLE I
Haemodynamic efects of dextrose, saline, and mannitol* Group
Control Dextrose Control Mannitol Control Dextrose Control Saline Control Mannitol Control Saline
No.
6 6 6 6 5 5 6 6 6 6 6 6
Systolic pressure (mnr Hg)
Diastolic pressure (mm Hg)
Mean arterial pressure (mm Hg)
145k7 14227 13754 160+8t 12957 133+8 134k12 148k4 12354 146t9f 136+11 13257
98+8 96+7 89k4 106+6t
118+8 113+7 107+4 130+6t 10656 11356 111f8 112+9 101 + 5 11658$ 101 + 6 107 k 7**
Results are mean + SEM.
t p < 0~005. $ p < 0.001. *+ p < 0.05.
8555
91f4 9459 97+8 8355 9455$ 83+6 90+8
Left aentricular end-diastolic pressure (cni H,O)
45I 4+ 1 2+13 6+2t 451 7+2 4+ I 1+1 3*1 551.5 2+1 2k1
Cardiac output (l.!min)
Haematocrit
2.520.2 2.7k0.2 2.550.2 3.2 + 0.2 2.6k0.2 2.7*0.2 3.5 5 0 . 2 3.6+0.2 3.3k0.2 3.6 5 0.2 3.4f0.2 3.5k0.2
34f2 33 + 2 33+2 29 + 3 t 3322 31+2 35 k 2 33+2 3352 29 2 t 31 + 3 31 5 2
(04)
+
Osinolality (mOsm)
310+2 306 k 3 302 k 2 325 31: 305 f5 303 f 5 306 5 2 308 + 3 305 + 3 327 2t 30552 305 f.2
+
+
Downloaded from by guest on June 6, 2016
Results Dextrose versus mannitol in conscious, intact dogs During the initial infusion of isotonic dextrose there was no significant alteration in systemic arterial pressure. During the second infusion of dextrose (the last study in each animal) there was also not a significant increase in mean arterial pressure (106k6 [SE] to 113k6 mm Hg). Mannitol increased mean aortic pressure from 107 f4 to 130 f 6 mm Hg (p < 0.005).With both dextrose and mannitol, there was a similar increase in left ventricular end-diastolic pressure of 3 f 1 cm H,O (Table 1) but this change was not statistically significant. Cardiac output tended to increase following mannitol from 2.5 f 0.2 to 3-1 kO.2 l./min but this change was not
significant. There was no significant change in cardiac output following either dextrose infusion (2-5 k 0.2 to 2.7 i-0.2 in the first study and 2.7 f 0.2 to 2-7 f0.2 in the second study). Maximal LV dp/dt increased with mannitol by 21% from 2,544f273 to 3,074f255 mm Hg/sec but was unchanged following both dextrose infusions (2,734 f 345 to 2,772 k 368 mm Hg/sec in the last infusion). dp/dt/p also increased following mannitol from 30.6f4-5 sec-l to 39.5 f 5.8 sec-l in the four animals in which this measurement could be made. The mean control total coronary blood flow to the right ventricle was 0.58 k 0.04 ml./min/g of tissue and the ratio of flow of the inner layer of the right ventricular free wall to the outer layer was 1.6. The control regional myocardial blood flows were determined using lZsI (15 p) microspheres. After mannitol, right ventricular coronary flow increased by 120% to 1.31 kO.7 ml./min/g of tissue with an inner: outer free wall ratio of 1.3. These regional myocardial blood flows and those for dextrose were made using 8 p microspheres. Dextrose did not change flow in the right ventricle to the same degree as that noted for mannitol (Tables 2 and 3). Control blood flow to the left ventricle was 0.99+0*09 ml./min/g of tissue and the inner: outer free wall ratio was 1.5. Following mannitol, flow increased by 113% to 2.22k0.21 ml./min/g of
50 Hutton, Marynick, Fixler, Templeton, and Willerson TABLE 2
Efect of dextrose, saline, and mannitol on regional myocardial blood flow* Inner-outer layer ratios Group
No.
Control Dextrose Mannitol Dextrose Control Saline Mannitol Saline
Right ventricle (ntl./min/g)
Left ventricle (ml./min/g)
Ventricular septum (ml./min/g)
Right ventricle
Left ventricle
Ventricular septum
0.58 f0.05 0.81 f O . 1 I
0.99 f 0.09 1.23 f 0.26 2.22 f 0.21 1 .I8 f 0.06 1.21 f0.12 1.37 f 0.1 5 2.01 fO.25$ 1.45f0.15
1.04 f0.06 1.36f0.24 2.31 f0.33 1.23 f0.23 1.24 f0.11 1.38f0.15 2 4 4 f0.24$ 1 5 6 + 0.18
I .6
I .5 1.4 I .6 I .7
I .4 1.4 1.5 1.5 1.4 1.5 1.4 1.3
1.31 f0.17 0.77 + 0.I 0.64 f 0.05 0.65 f 0.06 1.01 f0.09t 0.78 f 0.05
1.5 1.4 1.5 1.5 1.4 1.4 1.3
I .3 1.3 1.2 1.2
Results are means f SEM. Statistical comparisons were not made for the dextrose and mannitol group because of the small numbers involved. t p
Changes in regional coronary blood flow with hypertonic mannitol in conscious dogs’ I A N HUTTON, SAMUEL P . MARYNICK, D A V I D E. FIXLER, G O R D O N H . T E M P L E T O N , and J A M E S T . W I L L E R S O N
From the Pauline and Adolph Weinberger Laboratory for Cardiopulmonary Research of the Department of Internal Medicine, the Department of Pediatrics, and the Department of Physiology, Uniiiersity of Texas Southwestern Medical School at Dallas, Dallas, Texas, USA
Systemic haemodynamics and regional myocardial blood flow responses to hypertonic mannitol were studied in 10 conscious and 23 anaesthetized dogs. Mannitol infusion significantly increased regional myocardial blood flow in the conscious, intact dogs. Mannitol increased total coronary flow 20% in anaesthetized animals compared to 80% in the awake ones. In both groups mannitol exerted a significant positive inotropic effect as evidenced by increases in maximal LV dp/dt and dp/dt/p. These studies have also demonstrated that the intact conscious dog that has not received any sedation has an inner:outer wall left ventricular flow ratio greater than 1.0. AUTHORS’ SYNOPSIS
This study was supported by NHLI contract 72-2947. by NHLI research grant HL 15522, and by grants from the American Heart Association, Inc and the American Heart Association, Texas Affiliate, Inc. This work was performed during Dr Hutton’s tenure as a BritishAmerican Research Fellow of the American Heart Association and British Heart Foundation. His present address is: Department of Medical Cardiology, Royal Infirmary, Glasgow. Dr Willerson is an established investigator of the American Heart Association. 1
physiologically intact animals following hypertonic mannitol. In view of the potential clinical application of hypertonic mannitol, it was decided to assess its effects on both total and regional myocardial blood flow and ventricular function in conscious, intact dogs. This study presents an extension of previous observations in a more physiological preparation and provides new information regarding flow changes in the myocardium. In addition, the opportunity was taken to make certain comparisons between awake and anaesthetized dogs of the influence of hypertonic mannitol on myocardial function and coronary blood flow.
Materials and methods Ten adult mongrel dogs weighing 12-20 kg were anaesthetized with sodium pentobarbital (30mg/kg), intubated, and ventilated with a Harvard respirator using a gas mixture of 95% O2 and 5% C 0 2 .Sterile thoracotomies were performed through a left lateral incision. A calibrated solid-state pressure transducer (Konigsberg P21) with a frequency
Downloaded from by guest on June 6, 2016
It has been previously demonstrated that hypertonic agents exert a positive inotropic effect in both the anaesthetized dog (Wildenthal et al, 1969a) and in the isolated cat papillary muscle (Koch-Weser, 1963; Wildenthal et al, 1969b). Hypertonic mannitol has been reported to improve ventricular function and reduce myocardial damage while increasing total coronary blood flow during acute myocardial ischaemia in anaesthetized dogs (Willerson et al, 1972). Using isolated perfused canine hearts and a krypton washout technique, increases in collateral coronary blood flow have also been reported following hypertonic mannitol during acute myocardial ischaemia (Willerson et al, 1972). There have been no previous measurements of regional myocardial blood flow in
48 Hutton, Marynick, Fixler, Templeton, and Willerson
+
a small Holter pump with each microsphere injection. At the conclusion of the study the heart was removed, cut into right and left ventricles and ventricular septum, and each region subsequently dissected into inner or subendocardial, middle, and outer or subepicardial regions. The different regions of the heart and the reference blood samples were placed into separate scintillation vials and counted in a well scintillation detector (Nuclear Chicago). Regional myocardial blood flow was determined from the equation: myocardial flow myocardial nuclide activity reference sample flow . reference sample nuclide activity The radioactivity emitted from each nuclide was determined by the method of Rudolph and Heymann (1967) modified by using the reference sample technique to calculate flows and using different calibration constants for differential spectrometry. Arterial blood samples were taken at regular intervals for blood gas determination (Instrumentation Laboratories model 31 3), haematocrit (International Company microhaematocrit), and osmolality measurement (Fisk osmometer freezing point determination)l. The contractile state of the heart was assessed by determining the maximal rate of left ventricular pressure rise (dp/dt max) and the quotient of dp/dt and developed left ventricular pressure (dp/dt/p) during isovolumic contractions (Mason et a/, 1971). The dogs were trained to lie unsedated in a cradle and the study was not commenced unless the heart rate was less than 130 per minute. Each animal was atrially paced at a rate of 10-20 beats above his own heart rate. After initial measurements, either isotonic saline or dextrose was infused into the superior vena cava using a Harvard constant infusion pump at a rate of 7.6 ml./min for 20 min and then 3.8 ml./min for an additional 10 min. Pressures were continuously monitored. Cardiac output and myocardial blood flow were measured at the end of each infusion. The animal was allowed to recover over a 1 hr period and 25% mannitol was then infused into the superior vena cava at the previous rates of infusion. When the osmolality and haemodynamics had returned to the original steady state measurement, an average of 2+ hr after the administration of mannitol, either isotonic saline o r dextrose was infused again. In the anaesthetic studies, 23 adult mongrel dogs anaesthetized with chloralose (60 mg/kg) were similarly studied ; total coronary blood flow was measured from a 12 G polyvinyl catheter placed in 1
Range of error i 3 mom.
Downloaded from by guest on June 6, 2016
response greater than 1,000 Hz was introduced into the left ventricle through a stab incision near the apex. Pacing electrodes were sutured on both the left atrial appendage and on the right ventricle. A 15-gauge polyvinyl catheter was placed within the left atrial appendage. The pericardium was usually loosely resutured and the catheters and pacing wires were exteriorized at the back of the neck. The dogs were allowed 2-3 weeks to recover before being again anaesthetized with sodium pentobarbital and having 15-gauge polyvinyl catheters introduced into the superior vena cava and the thoracic aorta via the external carotid artery. All catheters were kept patent by intermittent flushing with heparin. Haemodynamic and coronary blood flow studies were performed 24 to 48 hr after insertion of the arterial and venous catheters. At the time of the study, left atrial and systemic arterial pressures were measured using Statham P23Db transducers and recorded on an Electronics for Medicine recorder. The zero reference point for both pressures was taken as midthorax with the dog lying in a cradle. The left ventricular end-diastolic pressure obtained from the solid-state transducer was adjusted so that it was equal to the mean left atrial pressure obtained from the internal left atrial catheter. The P21 Konigsberg transducer has a temperature error of 0.05 mm Hg/”C; there were no significant shifts in the stability of the Konigsberg transducer over the length of the acute experiments reported in this study. The left ventricular pressure was continuously differentiated using an R C differentiator to provide the rate of rise of pressure in the left ventricle, LV dp/dt. A cardiotachometer triggered by the electrical signal from the pressure pulse provided a precise measurement of heart rate which was kept constant by atrial pacing using a Grass S4 stimulator. Cardiac output was measured by the dye-dilution technique using indocyanine green dye as the indicator. The green dye was injected into the superior vena cava and blood withdrawn at a constant rate from the thoracic aorta through a densitometer and the dilution curve recorded (Lyons Medical Corporation). All outputs were done in duplicate and the mean of the results taken. The electrocardiogram was monitored continuously. Total and regional myocardial blood flows were measured using a radioisotope technique (Domenech ef d, 1969; Buckberg et a/, 1971). Microspheres, 8 ,u in diameter, labelled with 46Sc,*?3r, and 141Ceand lZ5l microspheres (15 IL in diameter) suspended in saline were used to measure the regional myocardial blood flow by alternately injecting a different microsphere into the left atrium. A reference blood flow sample was collected from the carotid artery in 30-sec fractions over a 2-min period using
49 Mannitol and total and regional myocardial blood flow
the coronary sinus and stabilized with suture ligation. Hypertonic mannitol (25%) or isotonic saline was administered intravenously at 3.81 ml./ min for 30 min. Regional myocardial blood flows were not measured in the studies on anaesthetized animals. The distal end of the coronary sinus catheter communicated with the left femoral vein and a 3-way stopcock allowed coronary sinus flow to be measured directly. Heart rate was kept constant by atrial pacing. Left ventricular, systemic arterial pressure, and LV dp/dt were measured. Statistical comparisons in all of the studies were made using the t test for paired data.
TABLE I
Haemodynamic efects of dextrose, saline, and mannitol* Group
Control Dextrose Control Mannitol Control Dextrose Control Saline Control Mannitol Control Saline
No.
6 6 6 6 5 5 6 6 6 6 6 6
Systolic pressure (mnr Hg)
Diastolic pressure (mm Hg)
Mean arterial pressure (mm Hg)
145k7 14227 13754 160+8t 12957 133+8 134k12 148k4 12354 146t9f 136+11 13257
98+8 96+7 89k4 106+6t
118+8 113+7 107+4 130+6t 10656 11356 111f8 112+9 101 + 5 11658$ 101 + 6 107 k 7**
Results are mean + SEM.
t p < 0~005. $ p < 0.001. *+ p < 0.05.
8555
91f4 9459 97+8 8355 9455$ 83+6 90+8
Left aentricular end-diastolic pressure (cni H,O)
45I 4+ 1 2+13 6+2t 451 7+2 4+ I 1+1 3*1 551.5 2+1 2k1
Cardiac output (l.!min)
Haematocrit
2.520.2 2.7k0.2 2.550.2 3.2 + 0.2 2.6k0.2 2.7*0.2 3.5 5 0 . 2 3.6+0.2 3.3k0.2 3.6 5 0.2 3.4f0.2 3.5k0.2
34f2 33 + 2 33+2 29 + 3 t 3322 31+2 35 k 2 33+2 3352 29 2 t 31 + 3 31 5 2
(04)
+
Osinolality (mOsm)
310+2 306 k 3 302 k 2 325 31: 305 f5 303 f 5 306 5 2 308 + 3 305 + 3 327 2t 30552 305 f.2
+
+
Downloaded from by guest on June 6, 2016
Results Dextrose versus mannitol in conscious, intact dogs During the initial infusion of isotonic dextrose there was no significant alteration in systemic arterial pressure. During the second infusion of dextrose (the last study in each animal) there was also not a significant increase in mean arterial pressure (106k6 [SE] to 113k6 mm Hg). Mannitol increased mean aortic pressure from 107 f4 to 130 f 6 mm Hg (p < 0.005).With both dextrose and mannitol, there was a similar increase in left ventricular end-diastolic pressure of 3 f 1 cm H,O (Table 1) but this change was not statistically significant. Cardiac output tended to increase following mannitol from 2.5 f 0.2 to 3-1 kO.2 l./min but this change was not
significant. There was no significant change in cardiac output following either dextrose infusion (2-5 k 0.2 to 2.7 i-0.2 in the first study and 2.7 f 0.2 to 2-7 f0.2 in the second study). Maximal LV dp/dt increased with mannitol by 21% from 2,544f273 to 3,074f255 mm Hg/sec but was unchanged following both dextrose infusions (2,734 f 345 to 2,772 k 368 mm Hg/sec in the last infusion). dp/dt/p also increased following mannitol from 30.6f4-5 sec-l to 39.5 f 5.8 sec-l in the four animals in which this measurement could be made. The mean control total coronary blood flow to the right ventricle was 0.58 k 0.04 ml./min/g of tissue and the ratio of flow of the inner layer of the right ventricular free wall to the outer layer was 1.6. The control regional myocardial blood flows were determined using lZsI (15 p) microspheres. After mannitol, right ventricular coronary flow increased by 120% to 1.31 kO.7 ml./min/g of tissue with an inner: outer free wall ratio of 1.3. These regional myocardial blood flows and those for dextrose were made using 8 p microspheres. Dextrose did not change flow in the right ventricle to the same degree as that noted for mannitol (Tables 2 and 3). Control blood flow to the left ventricle was 0.99+0*09 ml./min/g of tissue and the inner: outer free wall ratio was 1.5. Following mannitol, flow increased by 113% to 2.22k0.21 ml./min/g of
50 Hutton, Marynick, Fixler, Templeton, and Willerson TABLE 2
Efect of dextrose, saline, and mannitol on regional myocardial blood flow* Inner-outer layer ratios Group
No.
Control Dextrose Mannitol Dextrose Control Saline Mannitol Saline
Right ventricle (ntl./min/g)
Left ventricle (ml./min/g)
Ventricular septum (ml./min/g)
Right ventricle
Left ventricle
Ventricular septum
0.58 f0.05 0.81 f O . 1 I
0.99 f 0.09 1.23 f 0.26 2.22 f 0.21 1 .I8 f 0.06 1.21 f0.12 1.37 f 0.1 5 2.01 fO.25$ 1.45f0.15
1.04 f0.06 1.36f0.24 2.31 f0.33 1.23 f0.23 1.24 f0.11 1.38f0.15 2 4 4 f0.24$ 1 5 6 + 0.18
I .6
I .5 1.4 I .6 I .7
I .4 1.4 1.5 1.5 1.4 1.5 1.4 1.3
1.31 f0.17 0.77 + 0.I 0.64 f 0.05 0.65 f 0.06 1.01 f0.09t 0.78 f 0.05
1.5 1.4 1.5 1.5 1.4 1.4 1.3
I .3 1.3 1.2 1.2
Results are means f SEM. Statistical comparisons were not made for the dextrose and mannitol group because of the small numbers involved. t p
