J. Westby

Blood flow regulation during acute regional ischemia in feline hearts: Importance of postjunctional α1- and α1-adrenoceptors

Summary: Influence of postjunctional α1- and subsequent α2,-adrenergic antagonism on myocardial blood flow was measured in a group of anesthetized cats with acute occlusion of the left anterior descending coronary artery (LAD) and a control group (n = 10 for both). The relatively selective postjunctional α1-(doxazosin) and α2-adrenergic (SK& F 104078) antagonists were applied after β-adrenergic blockade (propranolol). Regional myocardial blood flow was obtained with radiolabeled microspheres. Major hemodynamic determinants for perfusion were kept constant both within and between groups by right atrial pacing and aortic obstruction. Mean coronary resistance in nonischemic myocardium was permanently lower in the occlusion group as compared with controls (p < 0.01). Subsequent α2-adrenergic antagonism reduced mean coronary resistance in controls only (p < 0.05). Cardiac output (CO) and dP/dt was reduced in LAD-occluded hearts after α2-adrenergic blockade (p < 0.01, p < 0.05). The study demonstrates the significance of postjunctional α2-adrenergic-mediated vasoconstriction in well-perfused myocardium of control hearts, whereas such vasoconstriction was deteriorated in LAD-occluded hearts. A role for myocardial α2-adrenoceptors for maintenance of global cardiac function in acute regional ischemia was also indicated.

Role of blood flow in protection against penetration of carcinogens into normal and healing rat gastric mucosa

The effects of intragastric capsaicin and gastric artery ligation on the penetration of the gastric carcinogenN[methyl-3H]-N′-nitro-N-nitrosoguanidine ([3H]MNNG) to proliferative cells were studied in normal and healing rat gastric mucosa. The percentage of S-phase cells labeled with [3H]MNNG in normal corpus mucosa was higher (7.0±2.0%) after gastric artery ligation than in controls with intact blood flow (2.7±1.0%) and in animals treated with capsaicin (1.8±0.5%). Corpus mucosal blood flow was correlated with the percentage of S-phase cells labeled with [3H] MNNG in normal controls and in capsaicin-treated animals. In healing corpus mucosa and in the antrum, capsaicin or gastric artery ligation did not affect carcinogen penetration. We conclude that blood flow protects against penetration of carcinogens to proliferative cells in normal corpus mucosa but not in the antrum. Low mucosal blood flow in the corpus could be a risk factor for initiation of gastric carcinogenesis.

Postjunctional α-Adrenergic Stimulation of Inotropy in Hypoperfused Myocardium Outside an Acute Infarct

Summary: The functional significance of myocardial postjunctional α-adrenergic support of inotropy in the vicinity of an acute regional ischemic zone was addressed in pentobarbital-anesthetized, β-adrenergic blocked cats with circumflex coronary artery occlusion. Regional myocardial performance was measured by ultrasonic crystals in the anterior wall perfused by the left anterior descending coronary artery (LAD) before and during postjunctional α-adrenergic antagonism (SK&F 104078 2 mg/kg). A group with unrestricted flow in the LAD (control group) was compared with a group perfused below the autoregulatory pressure range (stenosis group). End-systolic pressure–length relations during dynamic afterload elevation were calculated for assessment of regional contractility. Regional myocardial blood flow (RMBF) was measured by radioactive microspheres. SK&F 104078 did not alter regional myocardial shortening or the slope of end-systolic pressure–length relations in the control group. In the stenosis group, however, α-adrenergic antagonism produced significant deterioration of shortening as well as consistent reduction of the slope of the end-systolic pressure–length relations (p < 0.05). As a reflection of reduced demands for perfusion, impairment of midmyocardial and endocardial blood flow occurred in the stenosis group (p < 0.05). These findings imply a negative inotropic effect of SK&F 104078 in metabolically vasodilated myocardium in the vicinity of an acute ischemic region.

Myocardial adenine nucleotide depletion within 1 h of acute coronary artery occlusion

In anaesthetized open-chest casts with occlusion of the left anterior descending coronary artery (LAD), adenine nucleotides and degradation products were studied in small myocardial tissue samples (10-20 mg) with high-pressure liquid chromatography, and tissue blood flow was measured with radioactive microspheres 5, 10, 20, 40, and 60 min after LAD occlusion. There was a rapid and parallel decrease of myocardial ATP and accumulation of adenosine, inosine, hypoxanthine, and xanthine both in epicardial and endocardial half-layers of the ischaemic myocardium within the first 20 min of coronary occlusion. After 40 and 60 min, myocardial ATP content decreased and degradation products accumulated further in the endocardium but stabilized epicardially. Analysis of covariance showed that the slightly higher blood flow in ischaemic epicardial layers, did not explain the transmural difference in ATP content after 40 and 60 min. Adenosine decreased after 40 min of ischaemia in both wall layers reaching negligible amounts after 60 min. It is concluded that breakdown of energy stores is less severe in epicardial than in endocardial wall layers during the first hour after acute coronary occlusion in the cat heart. This transmural difference cannot be explained entirely by less severe epicardial ischaemia. Therefore, transmural heterogeneity in metabolic function during severe ischaemia may also be important.

Negative Inotropic Effect of Propranolol Is Attenuated in Underperfused Feline Heart with an Acute Ischemic Region

Summary β-Adrenergic blockade alleviates myocardial ischemia, probably largely through heart rate (HR) reduction. We hypothesized that the negative inotropic effect of β-blockade, which is believed to be potentially dangerous, is attenuated in underperfused hearts with an acute coronary artery occlusion. We studied the effect of intravenous propranolol (1 mg/kg i.v.) in feline hearts with acute circumflex coronary artery (LCX) occlusion by cross-oriented segments in normally perfused and mildly underperfused left ventricular (LV) anterior wall. A control group (n = 10) was compared with a stenosis group (n = 9) in which the mean coronary perfusion pressure was reduced (91 ± 4 g vs. 136 ± 5 mm Hg, p < 0.01). End-systolic pressure-length (ESP-ESL) relations during dynamic afterload increase and preload reduction were calculated to evaluate regional inotropy. HR and LV peak systolic blood pressure (LVSP) decreased in both groups after β-blockade (p < 0.05). Subendocardial and mid-myocardial blood flow measured by radiolabeled microspheres decreased in the control group (p < 0.05) but was unchanged in the stenosis group. Systolic shortening of circumferential segments also decreased in the control group (p < 0.05) but was unchanged in the stenosis group. ESP-ESL relations of circumferential segments shifted markedly rightward in the control group, whereas a modest rightward shift was noted in the stenosis group. This study in feline heart with acute LCX occlusion showed an attenuated negative inotropic effect of β-blockade in underperfused LV anterior wall