Tris-hydroxymethyl aminomethane and sodium bicarbonate to buffer metabolic acidosis in an isolated heart model.

Abstract

Metabolic acidosis induces a decrease in the developed force of cardiac muscle by affecting every step of the excitation--contraction coupling pathway. Due to transient worsening in intracellular acidosis, the value of administering sodium bicarbonate therapeutically during acute acidosis has been questioned. An alternative therapeutic drug, Tris-hydroxymethyl aminomethane (THAM) has the advantage of diffusing into the intracellular space. This study was designed to evaluate the effects of metabolic acidosis on myocardial performance and to determine the effects of alkalinization with sodium bicarbonate, THAM, and their combination. Using a blood-perfused isolated heart preparation, left ventricular contractility and relaxation were measured at normal pH and during metabolic acidosis (pH = 7.0). Acidosis dramatically impaired myocardial contractility and relaxation. After buffering with sodium bicarbonate, although plasma bicarbonate concentration was normalized, pH remained below normal owing to an increased PaCO2. Contractility and relation were initially worsened, then slightly improved to return to control values. THAM uncompletely buffered acidosis but significantly improved contractility and relaxation. The combination of THAM with sodium bicarbonate perfectly buffered acidosis without modifying PaCO2 and significantly improved contractility. The combination of THAM with sodium bicarbonate is based on the ability of THAM to capture the CO2 produced by the sodium bicarbonate buffer. This combination achieves a perfect correction of metabolic acidosis and improves myocardial performance.

Impact of buffering hypercapnic acidosis on cell wounding in ventilator-injured rat lungs

“…There is strong animal data suggesting the many potential benefits of hypercapnic acidosis (3,11,22,24), recently augmented by secondary analysis of the ARDSNet data (12). On the other hand, skepticism persists among some, with experimental and clinical data touting drawbacks to hypercapnic acidosis (16) and benefits of various buffering strategies (17,23,28), with some compelling clinical arguments for the use of THAM.…”

“…Bicarbonate buffers react to liberate carbon dioxide, which, because of high membrane permeability, may raise concern for further intracellular acidosis (9), a potentially operative, although unproven, mechanism in studies demonstrating worsened lung barrier function with buffering of hypercapnic acidosis (13,18). Tris-hydroxymethyl aminomethane (THAM), acting as a proton acceptor independent of carbon dioxide pathways, has been shown in animal and clinical models to reverse cardio-depressant effects attributed to hypercapnic acidosis (21,23,28).…”

Effects of acute hypercapnia with and without acidosis on lung inflammation and apoptosis in experimental acute lung injury

“…Animals were randomly allocated to three groups (n = 7 per group): (1) normocapnia (NC) -mechanically ventilated as described above to maintain PaCO 2 between 35 and 45 mmHg; (2) hypercapnia (HC) -mechanically ventilated with a gas mixture containing 5% CO 2 , 21% O 2 , and balanced N 2 (Linde Gas Therapeutics, Lidingö, Sweden) to maintain PaCO 2 between 60 and 70 mmHg; and (3) buffered hypercapnia (BHC) -mechanically ventilated with a gas mixture containing 5% CO 2 , 21% O 2 , and balanced N 2 (Linde Gas Therapeutics, Lidingö, Sweden) to maintain PaCO 2 between 60 and 70 mmHg. After 5 min, a bolus of sodium bicarbonate solution (8.4%) was given intravenously equivalent to one-third of the dose calculated according to the following equation: HCO 3 − (mEq) = 0.3 × weight (kg) × base excess (BE) (Sirieix et al, 1997). The remaining seven animals were not mechanically ventilated (NV) and were used for measurement of lung histology and molecular biology analysis (Fig.…”

Adjunctive therapies in sepsis: An evidence-based review

“…In isolated animal hearts perfused with acidic solutions, bicarbonate fails to augment ventricular contractility (70,82). In whole animals, the studies uniformly showed increased PaCO 2 and decreased pHi in different organs (62,83), augmented production of lactic acid (61,62,84), and failed to reveal any hemodynamic benefit for sodium bicarbonate when compared with iso-osmolar saline solution, regardless the extracellular pH and lactate concentrations (61,62,84,85).…”