David R. Salter

Triiodothyronine-enhanced left ventricular function after ischemic injury

Hypothyroidism is associated with profound left ventricular dysfunction. Brain-dead organ donors and patients undergoing cardiopulmonary bypass are chemically hypothyroid with significantly reduced circulating free triiodothyronine (T3). To test the hypothesis that T3 enhances left ventricular function in a hormonally deficient environment, a total of 36 healthy New Zealand White rabbit hearts were studied using a modified Langendorff preparation with Krebs-Henseleit perfusate and intra-ventricular balloon. In 9 normal rabbit hearts a cumulative dose-response curve with logarithmically increasing doses of T3 was obtained. The vehicle solution for T3 dissolution served as control (n = 9). Left ventricular function was assessed from peak developed pressure at baseline and after T3 administration. Triiodothyronine had no effect in normal hearts on peak developed pressure or end-diastolic pressure. In 18 rabbits, the acute effect of T3 administration after ischemia was investigated. Preischemic left ventricular function was measured to serve as baseline, and hearts were subjected to 37 degrees C global ischemia. Triiodothyronine (n = 9) or vehicle (n = 9) was infused during reperfusion, and left ventricular peak developed pressure was measured at 30 and 60 minutes of reperfusion. Recovery of function (expressed as percent return of left ventricular peak developed pressure) was significantly improved within 15 minutes of reperfusion (65.0% +/- 2.1% versus 80.2% +/- 4.1%) and remained significantly improved throughout the reperfusion period (p less than 0.05 by analysis of variance). These data suggest that although T3 possesses no inotropic properties, it significantly improves postischemic left ventricular function. The rapidity of the functional improvement suggests that these effects may be due to plasma membrane-mediated mechanisms.

Quantification of the contractile response to injury: assessment of the work-length relationship in the intact heart.

We used a sonomicrometric determination of ventricular dimension to examine the effect of ischemia and reperfusion on the work-length relationship in the intact heart to develop a useful and precise variable of ventricular contractile response to injury. Twenty anesthetized dogs were instrumented with epicardial ultrasonic dimension transducers to record right ventricular free wall chord length and left ventricular minor-axis length, micromanometers to record ventricular pressures, and an electromagnetic probe to record pulmonary arterial (n = 8) or aortic (n = 7) flow. Dogs were subjected to either 20 min (n = 7) or 30 min (n = 13) of global cardiac ischemia supported by cardiopulmonary bypass. Data were acquired over a range of end-diastolic volumes produced by transient (5 to 10 sec) vena caval occlusion before and after ischemia. In both ventricles, systolic epicardial dimensional shortening correlated with flow probe-measured stroke volume (mean r = .969) and regional stroke work calculated as the integral of instantaneous ventricular pressure and epicardial dimension correlated with measured global stroke work (mean r = .960), confirming the validity of dimensional measurements. Regression analysis demonstrated a highly linear relationship between calculated regional stroke work and end-diastolic length in the right ventricle (mean r = .973) and left ventricle (mean r = .967), quantifiable by a slope (Mw) and x intercept (Lw). Change in afterload produced by pulmonary arterial or aortic constriction resulted in no significant changes in Mw or Lw in either ventricle. Ischemia and reperfusion decreased Mw and shifted Lw to the right in both ventricles. The decrease in Mw with 30 min ischemia exceeded the decrease with 20 min ischemia by 29% in the right ventricle and by 32% in the left (p less than .04) with up to 1 hr of reperfusion. Changes in Lw were not related to severity of injury. After ischemia, infusion of calcium increased Mw by 177% in the right ventricle and by 67% in the left (p less than .03) without significant changes in Lw. Independent of load conditions, the slope Mw, of the linear stroke work vs end-diastolic length relationship is a valid and precise index of right and left ventricular contractile response to global ischemia in the intact circulation. This variable may be useful in evaluating therapies designed to limit myocardial injury and enhance ventricular functional performance.

Triiodothyronine (T3) and Cardiovascular Therapeutics: A Review

Hypothyroidism is associated with an abnormal hemodynamic state characterized by decreased heart rate, stroke volume, output, and contractility, and increased systemic vascular resistance. Since cardiopulmonary bypass (CPB) and surgical stress can induce profound decreases in triiodothyronine (T3) levels, the hemodynamic consequences of “stress‐induced” hypothyroidism and T3 repletion are of increasing clinical interest. Available data generally support the likelihood of a beneficial effect associated with T3 replacement in brain‐dead organ donors and in cases of low cardiac output following CPB. Although hypotheses have been advanced to account for these salutary effects, the mechanism by which T3 may augment hemodynamic performance has not been precisely defined, particularly in the acute setting. Although additional research is needed to clarify these and other issues, preliminary findings with T3 replacement indicate that such investigation is warranted.

Atrioventricular Fistula: An Unusual Complication of Endomyocardial Biopsy in a Heart Transplant Recipient

Endomyocardial biopsy remains the primary method for diagnosis of cardiac allograft rejection. Generally, endomyocardial biopsy is considered a relatively safe procedure in heart transplant recipients. Complications that have been reported are related to catheter insertion and include carotid arterial puncture, prolonged bleeding, vasovagal reaction, ventricular tachyarrhythmias, and transient conduction abnormalities. Serious complications such as right ventricular perforation with cardiac tamponade may also occur. Most complications are usually without significant long-term sequelae. This report describes an unusual case of atrioventricular fistula between the right atrium and left ventricle that occurred during a routine endomyocardial biopsy in a heart transplant recipient. Sudden hemodynamic compromise developed in this patient soon after heart biopsy associated with hemodynamic picture of high-output heart failure. Right heart catheterization, including oximetry, peripheral venous contrast echocardiography, color flow Doppler studies, and transesophageal echocardiography confirmed the diagnosis of fistulous communication between the right atrium and left ventricle, most likely through the membranous interventricular septum. Conservative medical management resulted in striking clinical improvement within 48 hours commensurate with spontaneous closure of the right atrium-to-left ventricle fistula documented by hemodynamic and echocardiographic studies.