Effects of Propranolol on Regional Myocardial Function, Electrograms, and Blood Flow in Conscious Dogs with Myocardial Ischemia

Abstract

A B S T R A C T The effects of coronary occlusion and of subsequent propranolol administration were examined in 18 conscious dogs. Overall left ventricular (LV) function was assessed by measurements of LV pressure and dP/dt, and regional myocardial function was assessed by measurements of segment length (SL), velocity of SL shortening and regional myocardial "work", i.e., pressure-length loops in normal, moderately, and severely ischemic zones. Regional intramyocardial electrograms were measured from the same sites along with regional myocardial blood flow as determined by the radioactive microsphere technique. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reduction and graded elevation of the ST segment. Propranolol depressed overall LV function, function in the normal zone (work fell by 17+4%), and in the majority of moderately ischemic segments (work fell by 7±+-3%). In severely ischemic segments the extent of paradoxical motion and post-systolic shortening was reduced by propranolol. After propranolol regional myocardial blood flow fell in the normal zone (11+2%) and rose in the moderately (15+4%) and severely (63+10%) ischemic zones. Thus, in the conscious dog with regional myocardial ischemia, propranolol induces a redistribution of myocardial blood flow, with flow falling in normal zones and rising in moderately and severely ischemic zones. The improvement in perfusion of ischemic tissue was associated with slight but significant depression of shortening, velocity, and work in the moderately ischemic Dr. Vatner is an Established

Effects of Nitroglycerin and Propranolol on the Distribution of Transmural Myocardial Blood Flow during Ischemia in the Absence of Hemodynamic Changes in the Unanesthetized Dog

“…With open-chested dogs, Fam and McGregor (7) found that nitroglycerin increased collateral flow only if well-developed collateral vessels already existed. No increase in collateral flow was ob- (18) in conscious animals demonstrated an increase in collateral flow after total coronary occlusions of 15-40 min. An alternate mechanism by which blood flow to the ischemic areas can be augmented is by the transmural redistribution of coronary flow. In the presence of subendocardial ischemia, nitroglycerin has been demonstrated to cause a redistribution of flow away from the epicardium and toward the endocardium by Becker et al (13) in open-chested dogs and by Bache et al (10) in conscious animals.…”

“…In studies by Gross and Winbury (25), the heart rate in dogs was not allowed to decrease after propranolol, and no change in endocardial-epicardial blood flow distribution could be demonstrated. In the presence of ischemia, no redistribution of flow has been demonstrated in either open-chested (14) or conscious (18) animals, even when alterations occurred in heart rate and other hemodynamic variables. Therefore, the results ofthis study are consistent with previous measurements and indicate that propranolol does not exert a direct effect on the transmural penetrating arteries.…”

Changes in ischemic blood flow distribution and dynamic severity of a coronary stenosis induced by beta blockade in the canine heart.

“…The dog model developed to produce regional myocardial ischemia differs from others' 4,22 in which /3-adrenergic blocking agents were studied after total coronary artery occlusion, but resembles that of Tomoike et al,28 who studied the effect of propranolol in a partial coronary occlusion model in conscious dogs. In the present model, distal coronary pressures, stenosis and distal resistances and regional myocardial blood flow were measured so that potential mechanisms by which /-adrenergic antagonists attenuate ischemia could be determined.…”

The influence of beta‐adrenoceptor antagonists with and without intrinsic sympathomimetic activity on local wall motion abnormalities in patients with coronary heart disease.

“…The mechanisms by which ,B-adrenoceptor blockers improve hypokinetic regions remain a matter of speculation. Beside regional changes in perfusion (Aldermann et al, 1973;Simon et al, 1978;Pitt & Ross, 1969;Vattner et al, 1977) direct metabolic effects should be taken into consideration (Magee et al, 1980). With our protocol two questions remain unanswered:…”