AMERICAN COLLEGE OF CARDIOLOGY NEWS The following five abstracts are from the winning entries in the Young Investigators’ Awards Competition, 28th Annual Scientific Session, the American College of Cardiology, March 11-15, 1979, Miami Beach, Florida.
First Award
Honorable Mention
A BIOLOGICAL MODEL OF PARASYSTOLE. J. Jalife, M.D., and G.K. Moe, M.D., Ph.D., F.A.C.C., Masonic Med. Res. Lab., Utica, NY 13503. The electrotonic interactions of a parasystolit pacemaker with ventricular responses to the normal pacemaker across an area of depressed excitability were simulated in a model consisting of strands of canine Purkinje fibers mountea in a sucrose gap preparation. Experiments were conducted to study the patterns of ectopic activity that result from entrainment of the "ectopic" pacemaker (EP) on one side of the sucrose gap, by evoked responses (SN) in the other side of the gap. When one-way conduction ("entrance block") was established, manipulations of the SN frequency and of the impedance between the two outer chambers resulted in periods of silence, concealed or manifest bigeminy, trigeminy and quadrigeminy, and periods of more complex patterns of group beating as the entrainment ratios changed. The results confirm the predictions of the previously described mathematical model that these patterns depend upon the magnitude of the electrotonic influence of SN on the EP cycle length and also upon the ratio of the intrinsic frequencies. These studies should help to distinguish between reentrant and parasystolic mechanisms in clinical arrhythmias.
INTERACTION BETWEEN CARDIAC AND SINOAORTIC BARORECEPTORS IN THE CONTROL OF EFFEPJZNT CARDIAC SYMPATHETIC NERVE ACTIVITY DURING MYOCARDIAL ISCHEMIA IN DOGS. Robert B. Felder, M.D. and Marc D. Thames, M.D., University of Iowa, Iowa City, Iowa 52242. The purpose of this study was to determine the relative influence of arterial baroreceptors(BR)and of cardiac receptors with vagal afferents and with sympathetic afferents on efferent cardiac sympathetic nerve activity(CSNA) during coronary artery occlusion(CA0). Changes in heart rate(HR in beats/min), arterial pressure(AP in mmHg), and integrated CSNA(% change from control; recorded from the cut central end of the left ventral ansa subclavia)were determined during transient(90 set) circumflex (Cx) and anterior descending(LAD)CAO before and after vagotomy (V). Before V dogs with carotid and aortic BR intactshoweda
similarincrease(mean+SE)in CSNA during Cx(7klX)andLAD (7+3%)occlusions in spite of a significantly greater fall in AP during Cx(-18tl)than during LAD(-7+2)CAO. HR did not change during these occlusions. During Cx CA0 dogs with sinoaortic denervation had decreases in CSNA(-17% 2%), AP(-5%4 mmHg), and HR(-17k3 beats/minf. In these dogs LAD occlusion resulted in a smaller decrease in AP (-14+3 mmHg)with no change in CSNA or HR. In dogs with sinoaortic denervation and vagotomy Cx and LAD occlusion resulted in similar decreases in AP(-29f? and -2123 mmHg, respectively), and small and inconsistent changes in HR and CSNA. We conclude that cardiac receptors with vagal afferents exert an inhibitory influence on CSNA during myocardial ischemia, and that this influence limits the arterial BR mediated increases in CSNA resulting from ischemia-induced hypotension. Small changes in CSNA during CA0 with vagi and BR afferents sectioned suggest that in the dog cardiac receptors with sympathetic afferents do not exert a major influence on the sympathetic outflow to the heart during myocardial ischemia.
Second Award PATHOGENESIS OF MALIGNANT HYPERTENSION PRODUCED BY MILD PROGRESSIVE RENAL ARTERY STENOSIS Victor J. Dz~u, MD; Seymour Rosen, MD; A. Clifford Barger, MD, Harvard Medical School, Boston, MA To simulate development of human renovascular hypertension, mild daily progressive renal artery constriction (PRAC) was substituted for single stage constriction in the one-kidney Goldblatt dog. Surprisingly, all 11 dogs so treated developed malignant hypertension (MH) which persisted despite release of constriction. To induce hypertension, fluid was injected into an inflatable RA cuff to lower renal perfusion pressure (RPP) by 5 mmHg below preconstriction pressure each day for lo-14 days. However, as MAP rose, RPP returned toward control in hours. Thus, daily PRAC did not lead to sustained BA hypotension; in fact, by the 7th day RPP began to rise above control. With MH, MAP increased from 107 ? 4 to 204 i 11 mmHg while RPP increased to 130 ? 9 mnHg; plasma renin activity (PRA) rose from 1.0 * 0.1 to 30 f 5 ng AI/ml/hr. Plasma aldosterone concentration (PAC) parallelled PRA. I.V. administratfon of Teprotide (CEI) lowered MAP to control. Renal blood flow (RBF) and filtration rate (GFR) fell below control within 2-3 days and progressively declined with repeated PRAC. Intrarenal resistance (RR) was markedly elevated (>lO fold during MH) but was dramatically reduced with intrarenal blockade of converting enzyme. Despite cuff release, RBF and GFR continued to decline while PRA increased further. Initial moderate salt and water retention was followed by a marked natriuresis and diuresis (N and D) leading to weight loss, plasma volume (PV) contraction and hemoconcentration. Thus, mild PRAC without sustained RA hypotension leads to a vicious cycle with a progressive rise in PRA, increased RR, N and D with resultant fall in PV, - a process terminating in MH with severe vascular damage.
1066
May 1978
The Anmrtcan Journal of CARDIOLOGY
Honorable Mention EFFECTS OF RETROGRADE SYSTOLIC STRETCH OF ISCHEMIC MYOCARDIUM J. David Ogilby; Lorentz Preysz; Carl S. Apstein, MD,FACC Cardiac Muscle Research Lab, Boston University, Boston,MA To assess the effects of the paradoxical or retrograde systolic stretch which is imposed on fibers in ischemic regions, isolated globally ischemic rabbit hearts (balloon in LV) were paced at 180/min and subjected to 90 min of ischemia (I) at 37OC with or without imposed repetitive 180/&n systolic expansion (SE) of the LV balloon to a level which duplicated pre-I systolic LV pressure. Post-I recovery was assessed for 60 min. With severe I (~1% of control coronary flow) active contractions ceased within 2-3 min. Without SE (n=6), 40+6mm Hg contracture occurred during I; SE (n=6), completely prevented contracture during I. Post-I recovery of developed pressure without SE was 2724% vs 63?3% with SE (P
First Award
Honorable Mention
A BIOLOGICAL MODEL OF PARASYSTOLE. J. Jalife, M.D., and G.K. Moe, M.D., Ph.D., F.A.C.C., Masonic Med. Res. Lab., Utica, NY 13503. The electrotonic interactions of a parasystolit pacemaker with ventricular responses to the normal pacemaker across an area of depressed excitability were simulated in a model consisting of strands of canine Purkinje fibers mountea in a sucrose gap preparation. Experiments were conducted to study the patterns of ectopic activity that result from entrainment of the "ectopic" pacemaker (EP) on one side of the sucrose gap, by evoked responses (SN) in the other side of the gap. When one-way conduction ("entrance block") was established, manipulations of the SN frequency and of the impedance between the two outer chambers resulted in periods of silence, concealed or manifest bigeminy, trigeminy and quadrigeminy, and periods of more complex patterns of group beating as the entrainment ratios changed. The results confirm the predictions of the previously described mathematical model that these patterns depend upon the magnitude of the electrotonic influence of SN on the EP cycle length and also upon the ratio of the intrinsic frequencies. These studies should help to distinguish between reentrant and parasystolic mechanisms in clinical arrhythmias.
INTERACTION BETWEEN CARDIAC AND SINOAORTIC BARORECEPTORS IN THE CONTROL OF EFFEPJZNT CARDIAC SYMPATHETIC NERVE ACTIVITY DURING MYOCARDIAL ISCHEMIA IN DOGS. Robert B. Felder, M.D. and Marc D. Thames, M.D., University of Iowa, Iowa City, Iowa 52242. The purpose of this study was to determine the relative influence of arterial baroreceptors(BR)and of cardiac receptors with vagal afferents and with sympathetic afferents on efferent cardiac sympathetic nerve activity(CSNA) during coronary artery occlusion(CA0). Changes in heart rate(HR in beats/min), arterial pressure(AP in mmHg), and integrated CSNA(% change from control; recorded from the cut central end of the left ventral ansa subclavia)were determined during transient(90 set) circumflex (Cx) and anterior descending(LAD)CAO before and after vagotomy (V). Before V dogs with carotid and aortic BR intactshoweda
similarincrease(mean+SE)in CSNA during Cx(7klX)andLAD (7+3%)occlusions in spite of a significantly greater fall in AP during Cx(-18tl)than during LAD(-7+2)CAO. HR did not change during these occlusions. During Cx CA0 dogs with sinoaortic denervation had decreases in CSNA(-17% 2%), AP(-5%4 mmHg), and HR(-17k3 beats/minf. In these dogs LAD occlusion resulted in a smaller decrease in AP (-14+3 mmHg)with no change in CSNA or HR. In dogs with sinoaortic denervation and vagotomy Cx and LAD occlusion resulted in similar decreases in AP(-29f? and -2123 mmHg, respectively), and small and inconsistent changes in HR and CSNA. We conclude that cardiac receptors with vagal afferents exert an inhibitory influence on CSNA during myocardial ischemia, and that this influence limits the arterial BR mediated increases in CSNA resulting from ischemia-induced hypotension. Small changes in CSNA during CA0 with vagi and BR afferents sectioned suggest that in the dog cardiac receptors with sympathetic afferents do not exert a major influence on the sympathetic outflow to the heart during myocardial ischemia.
Second Award PATHOGENESIS OF MALIGNANT HYPERTENSION PRODUCED BY MILD PROGRESSIVE RENAL ARTERY STENOSIS Victor J. Dz~u, MD; Seymour Rosen, MD; A. Clifford Barger, MD, Harvard Medical School, Boston, MA To simulate development of human renovascular hypertension, mild daily progressive renal artery constriction (PRAC) was substituted for single stage constriction in the one-kidney Goldblatt dog. Surprisingly, all 11 dogs so treated developed malignant hypertension (MH) which persisted despite release of constriction. To induce hypertension, fluid was injected into an inflatable RA cuff to lower renal perfusion pressure (RPP) by 5 mmHg below preconstriction pressure each day for lo-14 days. However, as MAP rose, RPP returned toward control in hours. Thus, daily PRAC did not lead to sustained BA hypotension; in fact, by the 7th day RPP began to rise above control. With MH, MAP increased from 107 ? 4 to 204 i 11 mmHg while RPP increased to 130 ? 9 mnHg; plasma renin activity (PRA) rose from 1.0 * 0.1 to 30 f 5 ng AI/ml/hr. Plasma aldosterone concentration (PAC) parallelled PRA. I.V. administratfon of Teprotide (CEI) lowered MAP to control. Renal blood flow (RBF) and filtration rate (GFR) fell below control within 2-3 days and progressively declined with repeated PRAC. Intrarenal resistance (RR) was markedly elevated (>lO fold during MH) but was dramatically reduced with intrarenal blockade of converting enzyme. Despite cuff release, RBF and GFR continued to decline while PRA increased further. Initial moderate salt and water retention was followed by a marked natriuresis and diuresis (N and D) leading to weight loss, plasma volume (PV) contraction and hemoconcentration. Thus, mild PRAC without sustained RA hypotension leads to a vicious cycle with a progressive rise in PRA, increased RR, N and D with resultant fall in PV, - a process terminating in MH with severe vascular damage.
1066
May 1978
The Anmrtcan Journal of CARDIOLOGY
Honorable Mention EFFECTS OF RETROGRADE SYSTOLIC STRETCH OF ISCHEMIC MYOCARDIUM J. David Ogilby; Lorentz Preysz; Carl S. Apstein, MD,FACC Cardiac Muscle Research Lab, Boston University, Boston,MA To assess the effects of the paradoxical or retrograde systolic stretch which is imposed on fibers in ischemic regions, isolated globally ischemic rabbit hearts (balloon in LV) were paced at 180/min and subjected to 90 min of ischemia (I) at 37OC with or without imposed repetitive 180/&n systolic expansion (SE) of the LV balloon to a level which duplicated pre-I systolic LV pressure. Post-I recovery was assessed for 60 min. With severe I (~1% of control coronary flow) active contractions ceased within 2-3 min. Without SE (n=6), 40+6mm Hg contracture occurred during I; SE (n=6), completely prevented contracture during I. Post-I recovery of developed pressure without SE was 2724% vs 63?3% with SE (P
