Tissue acidosis: role in sustained arteriolar dilatation distal to a coronary stenosis.

Abstract

This study tested the hypothesis that myocardial tissue acidosis is responsible for maintenance of reduced arteriolar tone distal to a severe coronary arterial stenosis. Domestic swine (n=10) were instrumented with a coronary arterial stenosis that reduced vessel diameter 80%. Measurements of hemodynamic indexes were made 1) before stenosis, 2) at 5, 20, and 60 minutes after stenosis placement, and 3) after each of three, 20-minute NaOH infusions (0.05 M, 0.1 M, and 0.5 M) distal to the stenosis (group 1). Intracellular pH at the end of 30 minutes of 0.5 M NaOH infusion distal to the stenosis was measured in a second group (n=6) of swine (group 2). After stenosis placement in group 1, endocardial blood flow declined significantly, and evidence of regional acidosis (increased coronary venous Pco2 and decreased coronary venous pH) and ischemia (lactate production) developed. One hour later, evidence of acidosis persisted, though to a lesser extent. Myocardial oxygen and lactate metabolism exhibited similar patterns. Infusion of 0.5 M NaOH (0.38 ml/min) reduced (p < 0.01) distal zone epicardial blood flow but did not change endocardial flow. Regional myocardial oxygen extraction (75 ±8%, mean+SD) and consumption (8.2+±2.3 ml/min/100 g) also declined significantly (p<0.01) in response to 0.5 M NaOH infusion compared with 60 minutes after stenosis (86±4 and 12.4+2.8 ml/min/100 g respectively). The pH of coronary venous blood (7.41+0.05) was elevated (p <0.01) by 0.5 M NaOH above prestenosis (7.36+±0.03) and 60-minute poststenosis levels (7.33+±0.04). Measurement of intracellular pH (14C-DMO/3H-inulin technique) in group 2 animals showed that distal zone pH (7.00±0.11) after 0.5 M NaOH infusion was at a level similar to that in normal myocardium in a nonstenosed region of the heart. Thus, because endocardial blood flow was unchanged during 0.5 M NaOH infusion, even though pH of coronary venous blood reached systemic levels and intracellular pH increased significantly, tissue acidosis is probably not required for maintenance of arteriolar dilation distal to a severe coronary arterial stenosis. The data support the hypothesis that tissue acidosis capable of mediating acute changes in coronary arteriolar tone does not have a major role in the long-term maintenance of reduced vascular tone distal to a coronary arterial stenosis. (Circulation 1989;79:890-898

Coronary Arteriolar Dilation to Acidosis

“…Recent studies indicated that K ATP channels 3 and PTX-sensitive G proteins 23 are involved in the coronary arteriolar dilation in response to hypoperfusion, ischemia, and increased metabolic demand, the conditions that are generally involved in tissue acidosis. 24 Our results suggested that activation of the K ATP channel through the PTX-sensitive G protein signaling pathway may contribute to the vasodilation observed during these metabolic disturbances. Under pathophysiological conditions such as hypercholesterolemia 25 and certain forms of hypertension, 26 the alteration of G protein function in vascular smooth muscle may have significant impact on the vasodilatory function of coronary arterioles in response to acidic stress, resulting in an inadequate flow and oxygen supply to the tissue during intense metabolic demands.…”

Comparison of 99mTc-teboroxime with thallium for myocardial imaging in the presence of a coronary artery stenosis.

“…A disproportionate increase in myocardial oxygen demand caused by both left ventricular dilation (mean left atrial pressure increased significantly) and the positive inotropic effects of phenylephrine likely was responsible.33 Subsequent reversal of lactate production with return to consumption during the recovery phase of the study is consistent with myocardial adaptation to prevailing oxygen supply/demand conditions and has been demonstrated previously. [3][4] Teboroxime redistribution was observed both at stress when lactate production occurred and at recovery when lactate production did not occur. The fact that lactate production was observed simultaneously with thallium redistribution in this study reflects that both imaging techniques are sensitive to stress-induced differences in regional coronary flow even though the mechanisms responsible for redistribution differ between the two.…”

“…A 3F angioplasty catheter was positioned in the mid-distal third of the anterior interventricular vein as described previously. 3,4 A plastic stenosis (7.5 -mm long; outer diameter, 3.5 mm; inner diameter, 0.625 mm) was then placed in the proximal one third of the left anterior descending artery. 34 The stenosis contained a second lumen into which the distal end of a 1.4-mm-diameter, 70-cm-long catheter had been attached before placement of the stenosis.…”