It has been known for over 100 years that acidosis decreases the contractility of cardiac muscle. However, the mechanisms underlying this decrease are complicated because acidosis affects every step in the excitation-contraction coupling pathway, including both the delivery of Ca2+ to the myofilaments and the response of the myofilaments to Ca2+. Acidosis has diverse effects on Ca2+ delivery. Actions that may diminish Ca2+ delivery include 1) inhibition of the Ca2+ current, 2) reduction of Ca2+ release from the sarcoplasmic reticulum, and 3) shortening of the action potential, when such shortening occurs. Conversely, Ca2+ delivery may be increased by the prolongation of the action potential that is sometimes observed and by the rise of diastolic Ca2+ that occurs during acidosis. This rise, which will increase the uptake and subsequent release of Ca2+ by the sarcoplasmic reticulum, may be due to 1) stimulation of Na+ entry via Na(+)-Ca2+ exchange; 2) direct inhibition of Na(+)-Ca2+ exchange; 3) mitochondrial release of Ca2+; and 4) displacement of Ca2+ from cytoplasmic buffer sites by H+. Acidosis inhibits myofibrillar responsiveness to Ca2+ by decreasing the sensitivity of the contractile proteins to Ca2+, probably by decreasing the binding of Ca2+ to troponin C, and by decreasing maximum force, possibly by a direct action on the cross bridges. Thus the final amount of force developed by heart muscle during acidosis is the complex sum of these changes.

Effects of changes of pH on the contractile function of cardiac muscle

Study objective To determine whether correction of acidemia using bicarbonate improves hemodynamics in patients who have lactic acidosis. Design Prospective, randomized, blinded, crossover study. Each patient sequentially received sodium bicarbonate and equimolar sodium chloride. The order of the infusions was randomized. Setting Intensive care unit of a tertiary care hospital. Patients Fourteen patients who had metabolic acidosis (bicarbonate less than 17 mmol/L and base excess less than -10) and increased arterial lactate (mean, 7.8 mmol/L). All had pulmonary artery catheters and 13 were receiving catecholamines. Measurements and main results Sodium bicarbonate (2 mmol/kg body weight over 15 minutes) increased arterial pH (7.22 to 7.36, P less than 0.001), serum bicarbonate (12 to 18 mmol/L, P less than 0.001), and partial pressure of CO2 in arterial blood (PaCO2) (35 to 40 mm Hg, P less than 0.001) and decreased plasma ionized calcium (0.95 to 0.87 mmol/L, P less than 0.001). Sodium bicarbonate and sodium chloride both transiently increased pulmonary capillary wedge pressure (15 to 17 mm Hg, and 14 to 17 mm Hg, P less than 0.001) and cardiac output (18% and 16%, P less than 0.01). The mean arterial pressure was unchanged. Hemodynamic responses to sodium bicarbonate and sodium chloride were the same. These data have more than 90% power of detecting a 0.5 L/min (7%) change in mean cardiac output after administration of sodium bicarbonate compared with that after sodium chloride. Even the 7 most acidemic patients (mean pH, 7.13; range, 6.90 to 7.20) had no significant hemodynamic changes after either infusion. Conclusions Correction of acidemia using sodium bicarbonate does not improve hemodynamics in critically ill patients who have metabolic acidosis and increased blood lactate or the cardiovascular response to infused catecholamines in these patients. Sodium bicarbonate decreases plasma ionized calcium and increases PaCO2.

Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study.

The mechanism by which the local effect of CO2ON pial arterioles is exerted was examined in anesthetized cats equipped with a cranial window for the direct observation of the microcirculation of the parietal cortex. The dilation of pial arterioles in response to application of artificial cerebrospinal fluid with low pH was the same whether or not the PCO2 of the solution was maintained in the normal range or markedly increased. The constriction of pial arterioles in response to application of artificial cerebrospinal fluid with high pH was the same whether or not the PCO2 of the solution was maintained in the normal range or markedly decreased. Finally, pial arterioles did not change their caliber in response to application of cerebrospinal fluid with unchanged pH but markedly increased or decreased Pco, or bicarbonate ion concentration. These results show that the action of CO2 on cerebral vessels is exerted via changes in extracellular fluid pH and that molecular CO2 and bicarbonate ions do not have independent vasoactivity on these vessels.

https://www.ahajournals.org/doi/pdf/10.1161/01.STR.8.3.358

Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels.

Function of the ventrolateral medulla in the control of the circulation

The effect of acidosis on Ca2+-activated force generation was studied in rabbit soleus, left ventricular, and adductor magnus muscles. Fibers were skinned (sarcolemma peeled off or mechanico-chemically disrupted) to facilitate direct manipulation and standardization of their intracellular ionic milieus according to bathing solution composition. Skinned single skeletal and small bundles of cardiac fibers were mounted in a photodiode force transducer and activated by immersion in buffered-Ca2+ bathing solutions. The magnitude of steady state isometric force at each [Ca2+] was determined at pH 7.0 and 6.5 (paired data) at both 1 mM and 10 mM Mg2+ in order to detect artifacts of errors in calculated [Ca2+]. All bathing solutions contained: 7 mM total EGTA [ethyleneglycol-bis-(β-amino-ethylether)-N,N′ tetra-acetic acid], 70 mM (Na++K+), 2 mM MgATP2− (Mg adenosine triphosphate), 15 mM CP2− (creatine phosphate), 15 units/ml CPK (creatine phosphokinase), imidazole (adjusted ionic strength to 0.15 M), and propionate anion at 23±1° C. Maximum tensions were similar at both [Mg2+]s but less at pH 6.5 than at pH 7.0, with the following order of mean magnitude of acidotic depression adductor>cardiac>soleus. The proportionately greater acidotic depression of submaximum (relative to maximum) forces that occurred only at 1 mM Mg2+ (cardiac>adductor>soleus) implicates acidotic depression of Ca2+-activated force as a major cause of decreased cardiac contractility.

ML Ng

Papers

Effects of changes of pH and of carbon dioxide tension on left ventricular performance.

Effects of myocardial hypoxia on left ventricular performance.

Cardiac response to cephalic ischemia.