Intraoperative transesophageal echocardiography.

Intraoperative echocardiography in patients undergoing cardiac surgery was first described in 1972. Interest in intraoperative echocardiography has grown in recent years due to the extensive information provided by 2-dimensional (2-D) and color-flow Doppler imaging via the transesophageal approach. The value of this technique also has been verified in large clinical studies involving patients undergoing cardiac surgery. Intraoperative transesophageal echocardiography (TEE) is very useful in preoperative formulation of surgical plans and in immediate post-operative assessment of surgical results in patients undergoing valve surgery.

Eight-year results of cyclosporine-treated patients with cardiac transplants.

To elucidate the long-term effects of cyclosporine, we retrospectively studied 310 consecutive patients who have undergone cardiac transplantation at our institution since December 1980 and in whom immunosuppression has been maintained with cyclosporine. The ages of recipients ranged from 1 month to 64 years and of donors from 1 month to 48 years. The actuarial survival rates for cyclosporine-treated patients were 80.7% at 1 year and 59.7% at 5 years and were significantly greater than those for previous patients not treated with cyclosporine (p less than 0.005). Their actuarial prevalence of rejection was 60.0% at 1 month and 86.9% at 1 year; 206 patients are living. The actuarial prevalence of lymphoma development was 4.6% at 5 years but has been significantly lower with the current immunosuppression protocol of lower doses of cyclosporine, and OKT3 in place of rabbit anti-thymocyte globulin (p less than 0.005). Infection remains the most common cause of death. Recipients less than 50 years of age had a significantly higher actuarial survival than older recipients (p less than 0.01). Male and female recipients had similar overall prevalence of survival and rejection, but men died of graft atherosclerosis significantly more frequently (p less than 0.005). Rehabilitation has been successful in 85% of patients surviving 1 year after transplantation. Of those surviving 1 year, 96.5% were in New York Heart Association class I. Thus the results of orthotopic cardiac transplantation have improved since the introduction of cyclosporine and have allowed measured liberalization of the criteria for recipient selection.

Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis.

We studied the effects of cytomegalovirus (CMV) infection on 301 cardiac transplant recipients who were treated during the cyclosporine era of immunosuppression (1980 to the present). These patients received varying combinations of cyclosporine, azathioprine, prednisone, rabbit antithymocyte globulin, and OKT3 as their immunosuppressive therapy. Two hundred ten patients were free of CMV infection (non-CMV group). During the same period CMV infection developed in 91 patients, as manifested by a fourfold IgG serologic titer rise, demonstration of CMV inclusion bodies in tissue, or positive cultures for the virus (CMV group). The rate of graft rejection was significantly higher in the CMV group. Graft atherosclerosis was significantly more severe in the CMV group as judged by angiographic criteria or by pathologic study. Patient survival rates were significantly lower in the CMV group. Death caused by graft atherosclerosis was significantly more common among patients in the CMV group. Finally, the graft loss rate (from either death or retransplantation for atherosclerosis) was significantly greater in the CMV group. These data demonstrate that CMV infection in cardiac transplant recipients is associated with more frequent rejection, graft atherosclerosis, and death.

Role of adenosine in coronary autoregulation.

The role of cardiac interstitial adenosine as an important metabolite in coronary autoregulation has not been established. We therefore measured steady-state cardiac interstitial adenosine concentration at a high and a low coronary inflow pressure using an epicardial diffusion well in anesthetized dogs. Although coronary resistance for the high and low pressure points showed highly significant differences (P less than 0.001), adenosine averaged 302 +/- 98 and 286 +/- 91 (SD) pmol/ml for the high and low pressure points, respectively (P greater than 0.20). Cardiac interstitial adenosine concentration was then measured with and without an intracoronary infusion of adenosine deaminase catalytic subunit. Adenosine averaged 28 +/- 21 (SD) pmol/ml during the infusion compared with 281 +/- 68 during control conditions (P less than 0.001). Finally, pressure-flow relations were obtained with and without the adenosine deaminase infusion, and there was no loss of autoregulation in the pressure of adenosine deaminase. These findings indicate that intracoronary adenosine deaminase markedly reduces interstitial adenosine concentration, that cardiac interstitial adenosine concentration remains constant during autoregulation, and that the coronary bed autoregulates normally when interstitial adenosine is reduced to levels close to zero. We conclude that cardiac interstitial adenosine concentration is not an important component in coronary autoregulation.

Transmural coronary flow reserve patterns in dogs.

To investigate transmural variations in coronary flow reserve, we studied 20 anesthetized dogs with a Gregg cannula in the left main coronary artery. In 11 dogs, radionuclide-labeled microspheres were injected over a range of perfusion pressures in the control state and during maximal coronary vasodilation produced with chromonar or adenosine. In another nine dogs, control, reactive hyperemic, and adenosine-vasodilated flows were compared at the same perfusion pressures. Adenosine dilated vessels more than did reactive hyperemia, which in turn vasodilated more than did hypoperfusion. Adenosine or chromonar vasodilated more than did hypoperfusion alone in all layers of the heart at perfusion pressures as low as 30 mmHg (P less than 0.05). This effect was greatest in the subepicardium and least in the subendocardium and varied with perfusion pressure (P less than 0.05). Subendocardial-to-subepicardial flow ratios declined with diminishing perfusion pressure despite the fact that flow reserve was present in all layers. We conclude that exhaustion of flow reserve is not the mechanism by which subendocardial ischemia occurs.

Effects of pressure gradients between branches of the left coronary artery on the pressure axis intercept and the shape of steady state circumflex pressure-flow relations in dogs.

When steady state pressure-flow relations are studied in the circumflex coronary artery, pressure gradients develop between it and other branches of the left coronary artery. To assess the effects of these pressure gradients, we compared the pressure axis intercept and shape of steady state circumflex pressure-flow relations in the presence and absence of gradients after autoregulation was abolished, both in the beating heart and during long diastoles in dogs. We used peripheral coronary pressures and radionuclide-labeled microspheres to assess arterial collateral flow. In the beating heart, interarterial pressure gradients reduced the curvature at low circumflex pressures, and overestimated the mean pressure axis intercept by 7.8 mm Hg (P less than 0.05). The results were similar for the pressure-flow relations derived during long diastoles. This overestimation exaggerates the difference between the pressure axis intercept and coronary sinus pressure. The peripheral coronary pressure and microsphere results indicate that these effects are mediated largely by arterial collateral flow.

The effects of cardiopulmonary bypass on coronary blood flow in the dog.

The effects of cardiopulmonary bypass on autoregulation, maximum coronary flow, and regional blood flow in the heart were investigated in 25 dogs. A Gregg cannula was inserted into the left main coronary artery, and pressure-flow relations were then measured in the autoregulating state or with vasodilation produced by intracoronary adenosine infusion before, during, and after cardiopulmonary bypass. Seventeen of the dogs had radioactive microspheres injected to investigate regional blood flow changes at the same times. (1) Autoregulation was not present after bypass for at least 3 hours. (2) Blood flow was shifted toward the subendocardium on bypass (increased subendocardial/subepicardial ratio) and tended to return to prebypass distribution following bypass. (3) Blood flow after bypass was not significantly different to the subendocardium and subepicardium. (4) Response to a coronary vasodilator (maximum coronary flow) was significantly affected by cardiopulmonary bypass: blood flow to all layers of the heart could be increased with adenosine after bypass. (5) Global lactate and oxygen metabolism were not adversely affected by bypass. We conclude that cardiopulmonary bypass abolished the normal autoregulation of coronary flow; this may predispose the incompletely revascularized patient to a "coronary steal" syndrome. However, the heart with normal coronary arteries is not underperfused in any layer after bypass. Thus, the bypass technique is not the cause of the subendocardial ischemia that sometimes complicates cardiac operations.

The effect of coronary inflow pressure on coronary vascular resistance in the isolated dog heart.

The shape of the coronary arterial pressure-flow relationship results from the interaction of a number of poorly understood physiological factors. Experiments in which coronary inflow and outflow pressures were coupled so that driving pressure was held constant showed that changes in inflow or outflow pressures altered coronary blood flow: coronary vascular resistance varied inversely with changes inflow pressure below 50 mm Hg and with changes in outflow pressure below 80 mm Hg. The magnitude of the influence of inflow pressure on resistance also depended on the fixed level of outflow pressure, the influence being large when the outflow pressure was low, and small when it was high. Inflow and outflow pressures, then, are two physiological factors which are determinants of the shape of the pressure-flow relationship, and their interaction contributes to the degree of curvature found in a particular relationship. These findings suggest that the use of linear regression in the interpretation of pressure-flow relationships results in poor estimation of resistance and zero-flow pressure. Other experiments measuring regional coronary blood flow using radionuclide-labeled microspheres resulted in the same inverse relationship between inflow pressure and resistance, regardless of mural depth, indicating that inflow pressure may influence resistance by distending vessels, rather than by causing sequential cessation of perfusion in successive transmural layers.