Coronary collateral circulation in the transplanted heart.

BACKGROUND: The concept that coronary collateral (CC) circulation can develop in cardiac transplant recipients (CTR) is controversial. Indeed, a decreased occurrence of CC in CTR has been previously reported. METHODS AND RESULTS: We reviewed 102 coronary angiograms in 73 CTR to evaluate the presence and significance of CC in denervated human hearts. These angiograms were compared with angiograms of 70 nontransplanted patients. Twenty-six CTR who had undergone at least two coronary angiograms, thus allowing comparative evaluations, form the basis for this study. Angiograms were analyzed using a modification of CC classification (Rentrop et al) from grade 0 for complete absence to grade 4 representing mature collateral with clear filling of epicardial vessels. Coronary artery disease was classified according to the scheme reported by Gao et al. For the purpose of this study, all type A lesions were grouped as large vessel disease (LVD), and types B1, B2, and C were collectively grouped as small vessel (epicardial) disease (SVD). The presence of CC circulation in all 73 CTR was grade 0, 7 (10%); grade 1, 41 (56%); grade 2, 33 (45%); grade 3, 30 (41%); and grade 4, 5 (7%). However, in control nontransplanted subjects grades 0, 1, 2, 3, and 4 were found in 47 (67%), 22 (31%), 4 (6%), 11 (15%), and 16 (20%) patients, respectively. The presence of mature collaterals (grade 4) in both groups were associated with type A lesions and was frequent in nontransplanted hearts. In contrast, grade 2 and grade 3 vascular channels probably representing CC with "myocardial blush" was more frequent in CTR and was mostly associated with small vessel coronary arteriopathy. CONCLUSIONS: These results suggest the presence of atypical CC in patients with cardiac allograft arteriopathy. It is speculated that this atypical form of CC with "blush pattern" may represent an angiogenic response to microvascular ischemia due to allograft coronary arteriopathy.

Effects of triiodothyronine supplementation after myocardial ischemia.

Cardiopulmonary bypass causes a "euthyroid-sick" state characterized by low levels of circulating triiodothyronine. Triiodothyronine supplementation in this setting has been postulated to improve postischemic left ventricular function by increasing the availability of myocardial high-energy phosphates. These postulates have not been substantiated, however, using load-independent parameters of left ventricular function and analysis of high-energy phosphate metabolism. To test these hypotheses, 14 healthy pigs (30 to 40 kg) were placed on cardiopulmonary bypass and instrumented with left ventricular minor-axis ultrasonic crystals and micromanometer-tipped pressure catheters. Hearts were subjected to 30 minutes of global, normothermic ischemia. Triiodothyronine (0.1 mg/kg; n = 7) or placebo (n = 7) was administered in a random, investigator-blinded fashion at the removal of the aortic cross-clamp and after 60 minutes of reperfusion. Hemodynamic, metabolic, and ultrastructural data were obtained before ischemia and after 30, 60, 90, and 120 minutes of reperfusion. By 90 minutes of reperfusion left ventricular contractility had returned to preischemic levels in hearts supplemented with triiodothyronine, despite postischemic myocardial adenosine triphosphate levels of 50% to 60% of baseline in both groups. Ultrastructurally, the sarcoplasmic reticulum and mitochondria were significantly better preserved in the group treated with triiodothyronine. This study suggests that triiodothyronine supplementation significantly enhances postischemic left ventricular functional recovery and that this recovery is due to mechanisms other than enhanced availability of myocardial high-energy phosphates.

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.

Prolonged hypothermic cardiac storage for transplantation. The effects on myocardial metabolism and mitochondrial function.

Cardiac storage for transplantation is currently limited to 6 hours. To better understand the metabolic changes that occur during hypothermic (4 degrees C) storage, we monitored the morphologic and metabolic changes in the canine myocardium at 0, 12, and 24 hours of storage in University of Wisconsin solution. Attempts to isolate cardiac mitochondria resulted in a progressive decline in the yield (milligrams of mitochondria per gram of heart tissue), which decreased (p less than 0.05) from 9.2 +/- 0.4 at 0 hours (control) to 4.0 +/- 0.3 after 12 hours and further decreased (p less than 0.05) to 1.9 +/- 0.2 after 24 hours of cold storage. Mitochondrial state 3 respiration fell to 64% of control after 12 hours and 28% of control after 24 hours of cold storage (p less than 0.05). Citrate synthetase activity, but not cytochrome C oxidase activity, was significantly depressed after 12 and 24 hours of cold storage. Adenosine triphosphate content decreased to 67% of control after 12 hours and 50% of control after 24 hours. After 12 hours of storage, sufficient adenosine diphosphate and monophosphate were present to permit some restoration of adenosine triphosphate, provided mitochondrial function was normal after transplantation. However, restoration of mitochondrial function and adenosine triphosphate levels sufficient to support myocardial contractility was unlikely after 24 hours of storage. This study suggests that a return of adequate cardiac function after transplantation may be possible after 12 hours of cold storage in University of Wisconsin solution but not after 24 hours of cold storage.

Measuring and managing quality of surgery. Statistical vs incidental approaches.

New rules for quality assurance provoked a comparison of effects of two approaches used concurrently for 14 years. In an incidental approach, a multidisciplinary conference reviewed all postoperative complications as they occurred and attributed each to one of six causes. Remedies were instituted and data were filed. In a statistical approach, death and complication rates were computed annually and compared with previous years' rates and with rates reported to Congress as national norms. Statistics suggested acceptable quality in each specialty but calculations were tedious and differences achieved significance too rarely or too slowly to identify problems, protect patients, and improve care. The incidental approach was popular and produced immediate improvements in patient care. Conferees attributed one half of complications to errors. Frequent acknowledgment of susceptibility to error may contribute to the safety and quality shown by our statistics.

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.

Radial artery infections and aneurysms after catheterization.

Twelve patients in whom radial artery infections developed after catheterization in an intensive care unit over a 2-year period were reviewed. The incidence of local infection was 0.4%. An increased risk of infection was associated with prolonged catheterization (greater than 4 days). Aneurysms developed in five patients. Signs of septic emboli were present in two patients, including Osler's nodes, Janeway's lesions, and fingertip infarcts. In 6 of the 12 patients, the radial artery infection resolved with antibiotic treatment alone. The five patients with infected aneurysms were treated successfully with antibiotics and surgical excision. The radial artery was reconstructed by use of a vein graft in one patient. We believe that patients not responding promptly to antibiotics or patients with infected aneurysms are best treated by surgical excision.

Myocardial infarction determined by technetium-99m pyrophosphate single-photon tomography complicating elective coronary artery bypass grafting for angina pectoris.

The incidence of acute myocardial infarction (AMI) complicating coronary artery bypass grafting (CABG) has previously been based on concordance of electrocardiographic, enzymatic and scintigraphic criteria. Technetium-99m pyrophosphate (Tc-PPi) single-photon emission computed tomography now enables detection of AMI with high sensitivity and specificity. Using this technique, perioperative AMI was detected in 12 of 58 patients (21%) undergoing successful elective CABG for stable angina pectoris. Stepwise multivariate logistic regression analysis was performed to compare the predictive value of preoperative (New York Heart Association class, left ventricular ejection fraction and use of beta blockers) and intraoperative (number of grafts constructed, use of internal mammary anastomoses, use of sequential saphenous vein grafts, smallest grafted distal vessel lumen caliber and aortic cross-clamp time) variables. Preoperative New York Association class (p = 0.04) and smallest grafted distal vessel lumen caliber (p = 0.03) were significant multivariate predictors of perioperative AMI. Only 1 perioperative patient with AMI (and 1 pyrophosphate-negative patient) developed new Q waves. Serum creatine kinase-MB was higher in patients with AMI by repeated measures analysis of variance (p = 0.0003). Five AMIs occurred in myocardial segments revascularized using sequential saphenous vein grafts, and 7 in segments perfused by significantly stenosed epicardial vessels with distal lumen diameter and perfusion territory considered too small to warrant CABG. At 6-month follow-up, the mean left ventricular ejection fraction increased from 0.61 to 0.65 in Tc-PPI-negative patients (p = 0.01), but not in perioperative patients with AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

The importance of load-independent analysis in assessment of the inotropic effect of prostaglandin E1 in vivo.

Load-independent pressure-dimension analysis was applied in 13 open-chest, anesthetized dogs during either left atrial (n = 7) or right atrial (n = 6) infusion of prostaglandin E1. Right atrial infusion of prostaglandin E1 in doses from 31 to 500 ng/kg/min resulted in no change in any parameters studied, including mean arterial pressure, cardiac output, and systemic and pulmonary vascular resistances. Left atrial infusion of prostaglandin E1 produced dose-dependent reductions in mean arterial pressure and systemic vascular resistance but no change in the slope of the relationship of left ventricular stroke work to end-diastolic length, a load-independent index of ventricular performance. In contrast to findings obtained with load-dependent parameters, these results suggest that prostaglandin E1 has no positive inotropic effect in vivo.

Ventricular function after atrial cardioplegia.

Continuous retrograde coronary sinus cardioplegia (CSCP) has previously been carefully evaluated experimentally and shown to be efficacious during ischemia, even in the presence of coronary lesions and in the hypertrophied state. A new technique of retrograde cardioplegia delivery through the right atrium, using right ventricular distension and pressures of 60 mm Hg, has recently been described with excellent clinical results. This study was designed to specifically examine right ventricular function after atrial cardioplegia and acute passive right ventricular distension. CSCP (n = 10) was compared with cardioplegia delivered through the right atrium both continuously (n = 10) and intermittently (n = 8). When ventricular function was examined with the use of the load-independent relationship of stroke work vs end-diastolic length, there was a profound deterioration of right ventricular function in both atrial cardioplegia groups (44% and 37% of control values, respectively) after 1 hr of reperfusion. In contrast, biventricular function was fully preserved in the CSCP group 1 hr after reperfusion. Left ventricular function measured at the end of reperfusion was preserved in all three groups. Right ventricular ATP levels were slightly but significantly depressed in all groups and in the atrial cardioplegia groups, this metabolic change was also seen in the left ventricle. These metabolic and hemodynamic data may reflect the inability of atrial cardioplegia to cool the myocardium below 16 degrees C. Postoperative right ventricular dysfunction may be more common than has been previously thought when atrial cardioplegia is used, particularly in the absence of topical cooling.

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.

Preload dependence of right ventricular blood flow: I. The normal right ventricle.

Right ventricular (RV) failure is commonly treated with intravascular volume expansion to increase the RV-left atrial pressure gradient and improve left-sided filling. As RV pressure rises, chamber distention occurs and wall tension increases. These studies were designed to determine if increased wall tension might impede RV myocardial blood flow in the normal canine right ventricle and thus contribute to RV failure. Hemodynamic data, the septal-RV free wall dimension, and RV myocardial blood flow were obtained at low and high levels of preload and in both the autoregulated and vasodilated (adenosine, 2 mg per kilogram of body weight per minute) states. Elevated filling pressure decreased RV myocardial blood flow in both the autoregulated (0.85 +/- 0.18 to 0.67 +/- 0.15 ml/min/gm; p less than .05) and vasodilated (2.25 +/- 0.50 to 0.85 +/- 0.25 ml/min/gm; p less than .05) states but did not change the transmural distribution of blood flow to the right ventricle. Vasodilator reserve was markedly impaired in the high-preload state. These observations suggest that preload is an important determinant of RV myocardial blood flow. Volume loading to treat RV dysfunction may be limited by impairment of RV myocardial blood flow.

The efficacy of blood versus crystalloid coronary sinus cardioplegia during global myocardial ischemia.

The efficacy of blood and crystalloid retrograde cardioplegia in protecting the ischemic myocardium was compared. Seventeen dogs underwent 2 hr of global myocardial ischemia while on cardiopulmonary bypass. Crystalloid (in nine dogs) or blood (in eight dogs) cardioplegic solution was infused continuously into the coronary sinus. Left and right ventricular function were assessed before ischemia and after 30 and 60 min of reperfusion by means of highly sensitive, load-independent index of contractility (the slope of the stroke work vs end-diastolic length relationship). Ventricular biopsies for ATP determination were obtained before ischemia, at the end of ischemia, and after 60 min of reperfusion. Left and right ventricular function returned to normal after 60 min of reperfusion in both groups. Left ventricular ATP remained unchanged, whereas small but significant decreases in right ventricular ATP were observed after 60 min of reperfusion in both groups. Thus continuous crystalloid or blood retrograde coronary sinus cardioplegia in dogs preserved myocardial function and metabolism equally well after 2 hr of global cardiac ischemia.

Myocardial protection.

Early studies of myocardial protection were designed to minimize ischemic injury. The next class and generation of investigations will most likely be designed to accelerate recovery following known myocardial injury. Such techniques will play an important role in allowing operations on acutely injured and ischemic myocardium and will be important in the treatment of postischemic injury when such injury occurs during the course of complex cardiac operations. Surgical aspects of myocardial metabolism are still rudimentary and many empiric observations require further exploration into the mechanisms by which such applications work.

Papillary-annular continuity and left ventricular systolic function after mitral valve replacement.

The contribution of the subvalvular apparatus to left ventricular function was evaluated in a canine preparation that allowed variation of subvalvular tethering forces after mitral valve replacement. Ten normal dogs were instrumented with micromanometer-tipped pressure catheters in the left ventricle and left atrium and piezoelectric sonomicrometry crystals to measure left ventricular major-axis, minor-axis, and wall thickness dimension changes. After control data were obtained, each dog underwent cardiopulmonary bypass and the mitral valve was replaced with a St. Jude bileaflet valve (No. 23 or 25). The native valve was completely excised and all chordal attachments were severed at the head of each papillary muscle. A 3-0 prolene suture was passed through the head of each papillary muscle, gently tied over a pair of felt pledgets, and exteriorized in a paravalvular manner that allowed both "attached" and "detached" states to be studied in a randomized manner 1 hr after release of the aortic cross-clamp. A significant (p less than .05) increase in major-axis length from control was observed in the detached state at both end-diastole and end-systole when compared at matched left ventricular end-diastolic pressures. Systolic function measured by load-dependent variables at matched end-diastolic lengths was higher in the detached state. However, when systolic function was examined by load-independent variables such as the slope of the stroke work end-diastolic length relationship, the slope of the end-systolic pressure-volume relationship, or the stroke work end-diastolic volume relationship, no statistically significant difference could be detected between states of papillary-annular continuity.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of needle aspiration in reducing the number of unnecessary breast biopsies.

The accuracy of the results obtained from 2334 open breast biopsies performed during a 9-year period at Mount Sinai Hospital in Toronto are reviewed. With meticulous follow-up and the liberal use of needle aspiration, the senior author (A.A.B.) noted a progressive increase in his malignant to benign ratio, from 18% in 1970 to as high as 56% near the end of the study. In contrast, the overall hospital ratio of malignant to benign breast biopsies obtained over the same decade remained stationary at 25%. A low ratio implies unnecessary hospital admissions and biopsies, all adding to the patient's anxiety. The authors conclude that a currently acceptable malignant to benign ratio is 1 to 3 and that with the use of fine-needle aspiration the number of surgical biopsies can be reduced, minimizing patient anxiety and morbidity, and increasing the efficiency of hospital bed use.