Martin M. Winbury

Intramyocardial diversion of coronary blood flow: Effects of isoproterenol-induced subendocardial ischemia

Abstract Isoproterenol was found to have produced adverse reactions in eight of our patients. All demonstrated large negative ST segment shifts. In experimental studies in rats, the J-shift of the electrocardiogram was sensitive to low doses of isoproterenol. Combined use of a nitrate and beta-blocker completely reversed the significant negative J-shift depression induced by isoproterenol. Dog studies using platinum electrodes to measure intramyocardial oxygen tension at the epicardium and endocardium documented an intracardiac diversion of blood flow between the subendocardium and subepicardium. Isoproterenol diverted blood flow away from the subendocardium, which is very vulnerable to ischemia and decreased perfusion. This isoproterenol-induced “coronary steal” is probably due to localized hypoxia at the subendocardium. Nitroglycerin and propranolol both selectively increased subendocardial blood flow with little effect at the subepicardium. The regulation of blood flow through the coronary circulation can be explained in part by an intramyocardial diversion phenomenon.

Intracoronary nitroglycerin, pentaerythritol trinitrate and dipyridamole on intramyocardial oxygen tension.

Abstract The effects of intracoronary injection of nitroglycerin, pentaerythritol trinitrate and dipyridamole on subepicardial (epi) and subendocardial (endo) oxygen tension were compared in anaesthetized open chest dogs. The P O 2 was determined simultaneously at a depth of 3 mm (epi) and 9 mm (endo) below the surface of the left ventricle with small platinum electrodes by a polarographic method. The two nitrates produced a selective increase in endo P O 2 , no change in epi P O 2 and a transient increase in coronary blood flow. In some cases, endo P O 2 increased in the absence of a significant rise in blood flow. Dipyridamole consistently caused a prolonged increase in coronary flow; epi P O 2 increased slightly and endo P O 2 decreased in some of the animals. Using data for nitroglycerin on P O 2 , regional blood flow and intercapillary distance, the changes in metabolism were predicted on the basis of the Krogh analysis. Metabolism was reduced in both epi and endo; P O 2 and blood flow were increased in endo and decreased in epi, and intercapillary distances were unchanged. It is concluded that the nitrates increase endo P O 2 of the left ventricle by a decrease in metabolism and redistribution of blood flow to endo from epi.

Effects of β-adrenoreceptor blockade and nitroglycerin on myocardial oxygenation

Abstract Small oxygen electrodes were used to determine oxygen tension (PO2) in the endocardial and epicardial regions of the left ventricle of dogs. The β-adrenoceptotor blocking agents propranolol, 1 mg/kg and bunolol (d,1-5-[3-(tert.- butylamino)-2-hydroxypropoxy]-3,4-dihydro-1(2H)-naphthalenone hydrochloride), 0.2 mg/kg, when administered i.v., produced a selective increase in endocardial PO2 in more than 60% of the animals. Epicardial PO2 was unchanged or decreased. The maximal increase in endocardial PO2 occurred within 5–10 min and persisted for at least 30 min. Coronary blood flow, heart rate and myocardial contractile force were reduced. Nitroglycerin, 20 μg/kg, i.v., also produced a selective increase in endocardial PO2 without a commensurate rise in epicardial PO2 in each of ten animals. It is proposed that the β-adrenoreceptor blocking agents and nitroglycerin produce the selective rise in endocardial PO2 by similar mechanisms, a decrease in myocardial metabolism and redistribution of coronary blood flow to improve perfusion of the endocardial region.

Pentaerythritol trinitrate and glyceryl trinitrate on intramyocardial oxygenation and perfusion in the dog. Krogh analysis of transmural metabolism.

1. The effect of intravenous pentaerythritol trinitrate and glyceryl trinitrate on left ventricular subepicardial (epi) and subendocardial (endo) Po2 and perfusion were compared in anaesthetized open‐chest mongrel dogs. Tissue Po2 was determined simultaneously at a depth of 3 mm (epicardial) and 9 mm (endocardial) with small platinum electrodes by polarography. In a separate series of dogs tissue perfusion of those regions was measured by hydrogen (H2) clearance using similar electrodes.

Differential effects of chromonar and nitroglycerin on intramyocardial oxygen tension

Abstract Tissue oxygen tension of the subepicardial (Epi Po2) and subendocardial (Endo Po2) regions of the canine left ventricular wall was determined polarographically. Chromonar consistently increased Epi Po2; Endo Po2 was decreased in half the studies and elevated in the other half. Coronary blood flow was maximally increased by chromonar and reactive hyperemia abolished. Nitroglycerin selectively increased Endo Po2 before and after chromonar. This suggests that arteriolar dilatation is not a requisite for the rise in Endo Po2 by nitroglycerin.

Pentaerythritol trinitrate and glyceryl trinitrate on myocardial oxygen consumption and haemodynamics in the dog

1. The effects of pentaerythritol trinitrate (pentrinitrol) and glyceryl trinitrate on myocardial oxygen consumption and myocardial and systemic haemodynamics were studied in anaesthetized open‐chest dogs. An in vivo oximeter in the coronary sinus permitted continuous determination of arteriovenous oxygen difference and myocardial oxygen consumption. All parameters were determined simultaneously at various intervals after drug administration.

Intravenous Saline Tolerance in Mice

Summary Mice tolerated intravenous injections of 5 cc per 20 g body weight of half physiological and physiological saline at maximum rates of 3.5 and 2.5 cc per minute respectively. The average lethal dose for physiological saline given at a rate of 0.9 cc per minute is 6.9 cc per 20 g.