The significance of the late fall in myocardial PCO2 and its relationship to myocardial pH after regional coronary occlusion in the dog.

Abstract

After acute regional coronary occlusion, myocardial tissue PCO2, as measured by mass spectrometry, rises, reaches a peak, and then gradually falls. This late fall in myocardial tissue PCO2 could be due to (1) a gradual increase in tissue blood flow (and hence improved carbon dioxide washout), (2) a gradual consumption of tissue bicarbonate, (3) a gradual reduction in the production of carbon dioxide due to progressive cellular damage, or (4) an artifact caused by the continued presence of the mass spectrometer probe in the ischemic tissue. To determine which of these four mechanisms is responsible for the late fall in myocardial tissue PCO2, we subjected 27 anesthetized open-chest dogs to 3-hour occlusion of the left anterior descending coronary artery. Both myocardial tissue PCO2 and intramyocardial hydrogen ion concentration were measured in the myocardial segment supplied by the left anterior descending coronary artery. Ten dogs (group 1) were killed after the occlusion (occlusion I), and 11 dogs (group 2) underwent reocclusion (occlusion II) at the same site after a 45-minute period of reflow. Regional myocardial blood flow was measured periodically by the intramural injection of 127Xe. Changes in myocardial tissue PCO2 and hydrogen ion concentration were related to ultrastructural changes in the tissues adjacent to the myocardial tissue PCO2 probe. Regional myocardial blood flow remained unchanged throughout the 3-hour occlusion, ruling out increased carbon dioxide washout as a cause for its late fall. Tissue hydrogen ion concentration, as measured by a new lead glass electrode, correlated well with myocardial tissue PCO2, with the reduction in regional myocardial blood flow, and with ischemic damage assessed histologically. Myocardial hydrogen ion concentration also exhibited a late fall after the occlusion, from a peak of 199.8 +/- 27.8 nmol/liter to 91.9 +/- 12.1 nmol/liter (mean +/- SEM). This ruled out consumption of tissue bicarbonate as the cause for the late fall in myocardial tissue PCO2. Peak rise in myocardial tissue PCO2 after occlusion II (71.2 +/- 7.9 mm Hg) was significantly lower than peak myocardial tissue PCO2 after occlusion I (116.7 +/- 13.9 mm Hg, P less than 0.001). The difference between these latter two values, as well as the magnitude of fall in myocardial tissue PCO2 during occlusion I, related directly to the degree of histological damage observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolic Correlates of Myocardial Stunning and the Effect of Cardiopulmonary Bypass

“…Mathemati cal modeling has demonstrated that following the first occlusion of this protocol, the increase in tissue PCO2 and [H+] far exceeds the levels predicted on the basis of decreased washout alone, indicating that an active production of COfe METABOLISM AND MYOCARDIAL STUNNING J CARD SURG 1993;8(Suppl):262-270 and [H +] occurs in response to the ischémie in sult. 5 In contrast, during the second occlusion in this model, the peak levels of myocardial PCO2 and [H +] do nor exceed the levels predicted on the basis of the decreased washout caused by the interruption of blood flow; i.e., there is no evidence of increased production of [H+] and CO2 during this occlusion. Hence, a metabolic correlate of postischemic cellular dysfunction is the inability of the myocardial cell to produce [H+] and CO2.…”

“…The late fall in both of these meta bolites is directly proportional to the magnitude of the ¡schemic insult and has been shown to be indicative of progressive cellular dysfunction. 5 When the occlusion is released at the end of 3 hours and reperfusion is allowed for 45 minutes, the increased washout restores the tissue PCO2 and [H+] to their preocclusion levels. During a second occlusion following this period of reper fusion, however, the rise in PCO2 and [H +] is sig nificantly lower than during the first occlusion.…”

Release and effects of calcitonin gene-related peptide in myocardial ischaemia

“…Wikström et al determined a 300% increase in tissue lactate, and a 50% decrease in pyruvate after 15 minutes occlusion of a coronary artery (Wikström et al, 1995). Ischaemia-induced metabolic disturbances correlate well with ischaemia-induced myocardial acidosis (Ichihara and Abiko, 1982;Khuri et al, 1985). In a canine model, 50% reduction of left anterior descending coronary artery (LAD) flow caused a significant fall in myocardial pH within 15 minutes (Shortt et al, 1997).…”

“…Furthermore, identical populations of C-fibres are activated in abdominal ischaemia with subsequent decrease in pH, and by lactic acid, but not by sodium lactate (Stahl and Longhurst, 1992). Ischaemia-induced metabolic disturbances correlate well with ischaemia-induced myocardial acidosis (Ichihara and Abiko, 1982;Khuri et al, 1985), and a reduction in extracellular pH to 5.5 has been demonstrated after acute coronary artery occlusion (Hirche et al, 1980). In preliminary studies in the pig models we have used, we recorded a pH value of 5.9 in the ischaemic zone after 35 min LAD occlusion.…”

Bicarbonato/CO2 aumenta dano em isquemia-reperfusão: da observação inicial à caracterização molecular

“…O tampão bicarbonato (HCO 3 -/CO 2 ), presente no ambiente intra quanto extracelular com concentrações de 14,5 e 25 mM, respectivamente, ainda é pouco estudado em processos redox apesar de estudos demonstrarem que ele estimula reações de oxidação, peroxidação e nitração em biomoléculas (Hodgson e Fridovich, 1976;Berlett et al, 1990;Radi et al, 1993;Zhang, 2000;Bonini e Augusto, 2001;Liochev e Fridovich, 2002;Stadtman et al, 2005;Trindade et al, 2006;Ezraty et al, 2011;Queliconi et al, 2013) e que sua concentração é aumentada até 4 vezes durante a isquemia (Khuri et al, 1985). Existem diversos mecanismos conhecidos que levam à produção do radical bicarbonato ( Fig.…”