A role for the renin-angiotensin system in the evolution of cardiac memory.
BACKGROUND
We studied the role of the cardiac renin-angiotensin II system in the genesis of cardiac memory, in which T wave changes induced by ventricular pacing (VP) accumulate and persist during subsequent sinus rhythm.


RESULTS
Anesthetized dogs were instrumented via a thoracotomy and three 20-minute runs of VP were interspersed with periods of normal sinus rhythm sufficient to permit T wave recovery to 90% of control. Memory was quantified as the change (delta) in T wave vector angle showing accumulation over the three monitoring periods. In five control dogs T wave vector = -27 +/- 49 degrees, and this shifted by 104 degrees (P < 0.05) over the three postpacing recovery periods. In seven dogs infused with the receptor blocker saralasin, five infused with the angiotensin-converting enzyme inhibitor captopril, and four infused with the tissue protease inhibitor chymostatin, there were significant reductions in the incidence and the accumulation of memory. In four other experiments, we used isolated, blood-perfused canine hearts to demonstrate that VP used to induce memory alters the contractile pattern of the left ventricle.


CONCLUSIONS
We propose that the alteration in myocardial stretch induced by pacing activates angiotensin II synthesis by cardiac cells. We propose, further that the endogenous cardiac renin-angiotensin II system (blocked by saralasin, captopril and by chymostatin) is an important contributor to the induction of memory.
Ricard
P
P
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Danilo
P
P
Cohen
I S
IS
Burkhoff
D
D
Rosen
M R
MR
D000804:Angiotensin II / Q000096:biosynthesis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010477:Perfusion; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012504:Saralasin / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D000804:Angiotensin II; C002101:chymostatin; D002216:Captopril; D012504:Saralasin