Acceptability and psychometric properties of the Minnesota Living With Heart Failure Questionnaire among patients undergoing heart valve surgery: validation and comparison with SF-36.

BACKGROUND: Health-related quality of life (HQOL) enhancement is a major objective of valvular surgery (VS), but assessments have been limited primarily to generic measures that may not be optimally responsive to intervention. Disease-specific instruments have been used in heart failure (HF), commonly associated with valve disease, but have been neither validated nor routinely applied among patients undergoing VS. METHODS AND RESULTS: We administered the Minnesota Living with Heart Failure (MLHFQ) and SF-36 questionnaires preoperatively (T(0)) to 50 patients undergoing VS and at 1 (T(1)) and 6 months (T(2)) after VS. Performance of MLHFQ was evaluated and compared with SF-36. MLHFQ completion rates were >98% (NS vs. SF-36); Cronbach's alpha was > or = 0.9 (total score, dimensions), supporting internal reliability. Confirmatory factor analysis verified good model fit for physical/emotional domain items (relative chi-squares < 3.0, critical ratios > 2.0, both instruments), supporting structural validity. Spearman coefficients correlating MLHFQ with parallel SF-36 domains were moderate to high (0.6-0.9; P < or = .001: T(0)-T(2)), supporting convergent validity. Baseline HQOL was poorest in patients with HF (P < or = .05 [both instruments]), supporting criterion validity. Responsiveness (proportional HQOL change scores: T(0) vs. T(2)) to VS was greater with MLHFQ vs. SF-36 (P < or = .002). CONCLUSIONS: Among patients undergoing VS, the MLHFQ is highly acceptable and maintains good psychometric properties, comparing favorably with SF-36. These findings suggest its utility for measuring disease-specific HQOL changes after VS.

Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease.

BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Definition of the safe lower limits of aortic resection during surgical procedures on the thoracoabdominal aorta: use of somatosensory evoked potentials.

The technique of intraoperative monitoring of somatosensory evoked potentials was applied to a canine model of spinal cord ischemia in an attempt to determine the safe lower limits of aortic resection during thoracic aortic surgery. Fifteen animals underwent left thoracotomy with institution of partial left atrial/femoral artery bypass for maintenance of distal aortic perfusion after proximal descending thoracic aortic exclusion. In Group I animals (n = 6, control), no further interventions were performed so that the effect of exclusion of vessels noncritical to spinal cord blood supply could be assessed by measurements of spinal cord blood flow and somatosensory evoked potentials. In Group II animals (n = 8), the level of distal aortic exclusion was progressively lowered until loss of somatosensory evoked potential (critical vessel exclusion) occurred. The effect of critical vessel exclusion on spinal cord blood flow was then assessed. Exclusion of multiple vessels noncritical to spinal cord blood supply (Group I) had no effect on spinal cord blood flow or function (somatosensory evoked potentials). Exclusion of vessels critical to spinal cord blood supply resulted in significant spinal cord ischemia (83.4% flow reduction, probability [p] less than 0.05 versus baseline) and ischemic spinal cord dysfunction (loss of somatosensory evoked potential).(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler echocardiography and computed tomography in diagnosis of left coronary arteriovenous fistula.

A 37 year old man with recurrent episodes of endocarditis was found to have a large left coronary arteriovenous fistula communicating with the right atrium. The origin and termination of the fistula were identified using computed tomography and two-dimensional Doppler echocardiography. Coronary angiography confirmed the diagnosis and the patient underwent a successful operation.

A comparison of three-year survival after coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty.

OBJECTIVES: The purpose of this study was to compare 3-year risk-adjusted survival in patients undergoing coronary artery bypass graft (CABG) surgery and percutaneous transluminal coronary angioplasty. BACKGROUND: Coronary artery bypass graft surgery and angioplasty are two common treatments for coronary artery disease. For referral purposes, it is important to know the relative pattern of survival after hospital discharge for these procedures and to identify patient characteristics that are related to survival. METHODS: New York's CABG surgery and angioplasty registries were used to identify New York patients undergoing CABG surgery and angioplasty from January 1, 1993 to December 31, 1995. Mortality within 3 years of undergoing the procedure (adjusted for patient severity of illness) and subsequent revascularization within 3 years were captured. Three-year mortality rates were adjusted using proportional hazards methods to account for baseline differences in patients' severity of illness. RESULTS: Patients with one-vessel disease with the one vessel not involving the left anterior descending artery (LAD) or with less than 70% LAD stenosis had a statistically significantly longer adjusted 3-year survival with angioplasty (95.3%) than with CABG surgery (92.4%). Patients with proximal LAD stenosis of at least 70% had a statistically significantly longer adjusted 3-year survival with CABG surgery than with angioplasty regardless of the number of coronary vessels diseased. Also, patients with three-vessel disease had a statistically significantly longer adjusted 3-year survival with CABG surgery regardless of proximal LAD disease. Patients with other one-vessel or two-vessel disease had no treatment-related differences in survival. CONCLUSIONS: Treatment-related survival benefit at 3-years in patients with ischemic heart disease is predicted by the anatomic extent and specific site of the disease, as well as by the treatment chosen.

Regional angiogenesis induced in nonischemic tissue by an adenoviral vector expressing vascular endothelial growth factor.

The feasibility of a single administration of a replication-deficient adenovirus (Ad) vector encoding the cDNA for human vascular endothelial growth factor (VEGF) (AdCMV.VEGF) to induce neovascularization in vivo in normal tissue was evaluated in retroperitoneal adipose tissue. Following administration of AdCMV.VEGF (10(9) pfu/50 microliters), maximal VEGF cDNA expression was observed at 2-5 days in the injected adipose tissue. No VEGF protein was detected at > or = 10 days in injected adipose tissue, and there was no increase in serum VEGF levels at any time. In vivo quantification of the number of blood vessels using 30x visualization of the adipose tissue demonstrated an increase in vessel number by 10 days, plateauing by 30 days with a 123% increase in vessel number compared to the control vector AdCMV.Null, despite the fact that no VEGF protein was detected after 5 days. Consistent with the in vivo data, histologic quantification of capillary number demonstrated an increase by day 5, reaching a 38% increase over AdCMV.Null by day 30. These observations demonstrate that an Ad vector carrying the VEGF cDNA is capable of inducing the growth of new blood vessels in a regional fashion in a relatively avascular, normal organ. This suggests in vivo Ad-mediated gene transfer may be useful for therapeutic angiogenesis in the treatment of ischemic cardiovascular disease.

Circumvention of anti-adenovirus neutralizing immunity by administration of an adenoviral vector of an alternate serotype.

Effective gene transfer and expression following repetitive administration of adenoviral (Ad) vectors in experimental animals is limited by anti-Ad neutralizing antibodies. Knowing that anti-Ad humoral immunity is serotype-specific, we hypothesized that anti-Ad neutralizing immunity could be circumvented using Ad vectors of different serotypes (Ad2, Ad5) within the same subgroup (C) to transfer and express beta-glucuronidase (beta glu) in the lung. Sprague-Dawley rats received an intratracheal administration of either Ad2 beta glu or Ad5 beta glu, and, 14 days later, repeat administration of either the same vector or a vector of a different serotype. Analysis of serum and bronchoalveolar lavage fluid following initial vector administration demonstrated systemic and local serotype-specific neutralizing antibodies. For both the Ad2 and Ad5 vectors, beta glu expression 24 hr following the second administration of the same serotype was < 30% of that of naive animals. In contrast, beta glu expression 24 hr following second administration of a different serotype Ad vector was similar to expression at 24 hr of naive animals receiving a single administration (Ad5 beta glu followed by Ad2 beta glu, as well as Ad2 beta glu followed by Ad5 beta glu; p > 0.2 both comparisons). Although the alternative serotype bypassed anti-Ad neutralizing immunity, persistence of expression was reduced compared to that following administration to naive animals. Compatible with this observation, systemic administration of the same vectors to C57B1/6 mice demonstrated induction of cytotoxic T lymphocytes directed against the beta glu transgene, as well as products of the Ad genome. Interestingly, intratracheal administration of vectors with different serotypes and different transgenes to rats resulted in longer expression (but still not normalized) compared to that achieved with vectors of different serotypes but the same transgene. These observations demonstrate that alternate use of Ad vectors from different serotypes within the same subgroup can circumvent anti-Ad humoral immunity to permit effective gene transfer after repeat administration, although the chronicity of expression is limited, likely by cellular immune process directed against both the transgene and viral gene products expressed by the vector.

Safety of direct myocardial administration of an adenovirus vector encoding vascular endothelial growth factor 121.

A gene therapy strategy involving direct myocardial administration of an adenovirus (Ad) vector encoding the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) has been shown to be capable of "biological revascularization" of ischemic myocardium in an established porcine model [Mack, C.A. (1998). J. Thorac. Cardiovasc. Surg. 115, 168-177]. The present study evaluates the local and systemic safety of this therapy in this porcine ischemia model and in normal mice. Myocardial ischemia was induced in Yorkshire swine with an ameroid constrictor 21 days prior to vector administration. Ad(GV)VEGF121.10 (10(9) or 10(10) PFU), Ad5 wild type (10(9) PFU), AdNull (control vector with no transgene; 10(9) PFU), saline, or no injection (naive) was administered in 10 sites in the ischemic, circumflex distribution of the myocardium. Toxicity was assessed by survival, serial echocardiography, blood analyses, and myocardial and liver histology at 3 and 28 days after vector administration. All pigs survived to sacrifice, except for one animal in the Ad(GV)VEGF121.10 (10(10) PFU) group, which died as a result of oversedation. Echocardiograms of Ad(GV)VEGF121.10-treated pigs demonstrated no differences in pericardial effusion, mitral valve regurgitation, or regional wall motion compared with control pigs. Intramyocardial administration of Ad(GV)VEGF121.10 included only minimal myocardial inflammation and necrosis, and no hepatic inflammation or necrosis. Only a mild elevation of the white blood cell count was encountered on day 3, which was transient and self-limited in the Ad(GV)VEGF121.10 group as compared with the saline-treated animals. As a measure of inadvertent intravascular administration of vector, normal C57/BL6 mice received intravenous Ad(GV)VEGF121.10 (10(4), 10(6), 5 x 10(7), or 10(9) PFU), AdNull (5 x 10(7) or 10(9) PFU), or saline. Toxicity was assessed by survival, blood analyses, and organ histology at 3 and 7 days after vector administration. A separate group of C57/BL6 mice received intravenous AdmVEGF164 (Ad vector encoding the murine VEGF164 cDNA), Ad(GV)VEGF121.10, AdNull (10(8) PFU each group), or saline to assess duration of expression and safety of a homologous transgene. All mice survived to sacrifice except for 40% of the mice in the highest (10(9) PFU; a dose more than 10(3)-fold higher by body weight than the efficacious dose in pigs) Ad(GV)VEGF121.10 dose group, which died on days 5-6 after vector administration. The only differences seen in the blood analyses between treated and control mice were in the very high Ad(GV)VEGF121.10 dose group (10(9) PFU), which demonstrated an anemia as well as an increase in alkaline phosphatase when compared with all other treatment groups. Hepatic VEGF levels by ELISA in AdmVEGF164-treated mice did not persist beyond 14 days after vector administration, suggesting that persistent expression of a homologous VEGF gene transferred with an Ad vector is not a significant safety risk. Although this is not a chronic toxicity study, these data demonstrate the safety of direct myocardial administration of Ad(GV)VEGF121.10, and support the potential use of this strategy to treat human myocardial ischemia.

Left ventricular pseudoaneurysm causing superior vena caval obstruction and effusive-constrictive pericarditis.

A diabetic woman with a silent myocardial infarction on clinical and electrocardiographic criteria presented with findings on physical examination of superior vena caval obstruction and effusive-constrictive pericarditis. A left ventricular posterior wall pseudoaneurysm and intrapericardial hematoma were found, with extrinsic compression of the right atrium. The diagnosis was first suspected by radionuclide imaging and confirmed by contrast angiography and surgery.

Pheochromocytoma of the heart.

This is a presentation of a unique case of cardiac pheochromocytoma during pregnancy. The case is significant because pheochromocytoma is a difficult diagnosis and its rarity during pregnancy may lead to this important diagnosis being overlooked, even though treatment is specific and highly successful.

Severe mitral regurgitation due to mitral valve prolapse: risk factors for development, progression, and need for mitral valve surgery.

Patients with mitral valve prolapse (MVP) may develop severe mitral regurgitation (MR) and require valve surgery. Preliminary data suggest that high body weight and blood pressure might add to the irreversible factors of older age and male gender in increasing risk of these complications. Fifty-four patients with severe MR due to MVP were compared with 117 control subjects with uncomplicated MVP to elucidate factors independently associated with severe MR: the need for valve surgery and the cumulative risk of requiring mitral valve surgery. Patients with severe MR were older (p<0.00005), more overweight (p = 0.002), had higher systolic (p = 0.0003) and diastolic (p = 0.007) blood pressures, and were more likely to have hypertension (p = 0.0001) and to be men (p<0.001). In both groups, men had higher blood pressure and relative body weight than women. In multivariate analysis, older age was most strongly associated with MR; higher body mass index, hypertension, and gender were independent predictors of severe MR in analyses that excluded age. Among the 54 patients with severe MR, the 32 (59%) who underwent mitral valve surgery during 11 years of follow-up were older, more overweight, and more likely to be hypertensive than those not requiring surgery. Among patients undergoing mitral valve surgery in 3 centers, mitral prolapse was the etiology in 25%, 67% of whom were men. Using these data and national statistics, we estimate that the gender-specific cumulative risk for requiring valvular surgery for severe MR in subjects with MVP is 0.8% in women and 2.6% in men before age 65, and 1.4% and 5.5% by age 75. Thus, subjects with MVP who are older, more overweight, and hypertensive are at greater risk for severe MR and valve surgery. Higher blood pressure and relative weight in men with MVP appear to contribute to the gender difference in risk for severe MR.

Monitoring of somatosensory evoked potentials during surgical procedures on the thoracoabdominal aorta. II. Use of somatosensory evoked potentials to assess adequacy of distal aortic bypass and perfusion after thoracic aortic cross-clamping.

Pulsatile left atrial-femoral artery bypass was instituted after aortic cross-clamping distal to the left subclavian artery in a canine experimental model to determine the relationship of distal aortic perfusion pressure with spinal cord blood flow and somatosensory evoked potentials. In six animals (Group I) distal aortic perfusion pressure was maintained at 100 mm Hg throughout a 1 hour interval of aortic cross-clamping. During this period, somatosensory evoked potentials and spinal cord blood flow (radioactive microspheres) showed no significant change from baseline. In six other dogs (Group II) distal aortic perfusion pressure was initially maintained at 100 mm Hg after aortic cross-clamping and then progressively decreased to 70, 40, and 25 mm Hg. Somatosensory evoked potentials and spinal cord blood flow were preserved at baseline levels for all distal perfusion pressures greater than 70 mm Hg. At 40 mm Hg, abnormalities in amplitude of the somatosensory evoked potentials were noted in all animals with progression to complete loss of evoked potential activity at lower perfusion pressures. Maintenance of adequate somatosensory spinal cord conduction after thoracic aortic cross-clamping is dependent on a critical level of distal aortic perfusion that can be accomplished by use of an adjunct such as pulsatile left atrial-femoral artery bypass. The critical level of distal aortic perfusion pressure to maintain normal somatosensory evoked potentials and spinal cord blood flow in this canine experimental study was 70 mm Hg or greater. Because inadequate distal aortic perfusion can be easily detected by monitoring of somatosensory evoked potentials, these techniques should prove helpful in evaluating the effectiveness of distal perfusion techniques during clinical aortic cross-clamping for procedures on the thoracoabdominal aorta.

Aneurysms of the descending aorta. Surgical experience in 48 patients.

Uniformity of opinion does not exist concerning an optimal surgical strategy for descending aortic aneurysms. In order to assess the impact of surgical technique on operative mortality, morbidity, late outcome, we reviewed 48 consecutive patients operated upon from 1976 to 1980. Average age was 61 years, and 37 patients (77%) were men. The average interval of aortic occlusion in the Gott shunt group was 48 minutes, which was significantly longer than that of patients operated upon without shunts (30 minutes). No patient in the Gott shunt group had postoperative paraplegia, but it was noted in two patients (18%) treated without a shunt. Operative deaths in patients with Gott shunts were caused by cardiac (two patients), neurologic (one patient), pulmonary (one patient), and abdominal (two patients) factors. A pulmonary embolus caused the single postoperative death in the "no shunt" group, and another patient died intraoperatively. A group of seven patients were treated by temporary femoral vein--femoral artery bypass because of extensive aneurysmal disease, advanced associated major systemic disorders, or anticipated excessive hemorrhage when the aneurysm was opened. All patients survived free of neurologic sequela, but one developed a reversible intraoperative coagulopathy. This study underscores the safety and usefulness of the femoral vein--femoral artery bypass in treating certain descending thoracic aneurysms and reinforces the importance of several technical guidelines concerning the proper insertion and use of the Gott shunt. These guidelines would have significantly reduced the observed operative morbidity and mortality.

Angina following myocardial revascularization. Does time of recurrence predict etiology and influence results of operation?

To assess the operative mortality and long-term results in patients undergoing repeat revascularization for recurrent angina, we analyzed 48 consecutive patients operated upon at New York University Medical Center between 1970 and 1978. Between January, 1970, and July, 1973, 15 patients underwent repeat revascularization with five operative deaths (33 percent). Thirty-three patients underwent similar operations from July, 1973, to July, 1978, with only one operative death (3 percent). Technical factors and improved methods of myocardial protection during the operation directly influence this decrease in operative mortality rate. The indication for reoperation was incapacitating angina developing within 2 months of the inital operation in 18 patients (early failures) and after more than 2 months in 30 patients (late failures). The early failures were most commonly attributed to technical factors (33 percent) and graft occlusion by exuberant pericardial scarring (33 percent). The late failures were commonly related to the development of new native coronary lesions (47 percent) and selection of an incorrect site for distal anastomoses (23 percent). The prognostic and therapeutic implications of these findings will be discussed in detail. Angina was abolished or significantly decreased in 90 percent of the survivors, and there were only two late deaths occuring 18 and 20 months postoperatively. These data indicate that patients undergoing repeat myocardial revascularization can be operated upon with low operative mortality rates and symptomatic improvement comparable to that of patients undergoing coronary artery bypass for the first time.

Coronary artery bypass with freeze-preserved saphenous vein allografts.

Over the past 5 years, 13 patients had coronary artery bypass performed with freeze-preserved saphenous vein allografts. There were no operative deaths or significant morbidity. Six patients were studied postoperatively at 42, 37, 10, 7, 5, and 1 months. Six of 8 grafts were patent with good flow. There were four late deaths; two of these occurred in patients who had concomitant resection of a ventricular aneurysm. Of the 9 surviving patients, 6 (6/9) are asymptomatic and 2 (2/9) have occasional chest pains; the condition of 1 patient (1/9) is unchanged. This experience suggests that free-preserved saphenous vein allografts may be used successfully for coronary bypass when autologous veins and internal mammary arteries are unavailable or insufficient for multiple bypass.

Aneurysms of the ascending aorta and transverse arch: surgical experience in 80 patients.

Aneurysms of the ascending aorta and transverse arch constitute formidable surgical challenges. To assess the impact of surgical techniques on operative morbidity and mortality and late results, we reviewed 80 consecutive patients operated from 1976 through 1980. Average age was 52 years and 81% were male. The operative mortality was 17.5% (14 deaths). In patients with aneurysm of the ascending aorta, operative deaths were due to cardiac factors (three patients), neurologic factors (three patients), cardiac factors (two patients), and exsanguination (one patient) accounted for the six operative deaths in patients with transverse arch aneurysms. Two late neurologic deaths occurred in this group. The following conclusions were reached when the surgical techniques were reviewed: Annuloaortic ectasia is best treated by insertion of a conduit with reimplantation of coronary ostia. Dissections are optimally managed by Dacron graft insertion in the ascending aorta and valve replacement. Aortic valve resuspension was done in six patients, with three undergoing subsequent aortic valve replacement for insufficiency. Aneurysms of the transverse arch treated with profound hypothermia and circulatory arrest were associated with fewer neurologic complications, and the operations were more expeditiously completed. Eleven of 80 patients (14%) had or subsequently needed additional surgical procedures on the aortic valve (insufficiency) or the distal aorta.

Benign tumors of right atrium necessitating extensive resection and reconstruction.

Two patients with gigantic benign right atrial tumors were successfully treated at New York University Medical Center. Both patients required extensive resection and reconstruction for cure. Although these tumors are rare, thorough exploration employing cardiopulmonary bypass is required before an appraisal of resectability can be made. Reconstruction can be readily accomplished with autologous pericardium and thereby provides an opportunity for cure of these unusual and rare lesions.

Experiences with the Carpentier techniques of mitral valve reconstruction in 103 patients (1980-1985).

A total of 103 patients, age range 2 to 77 years, had some type of Carpentier reconstruction for mitral insufficiency. The mitral insufficiency resulted from ruptured chordae in 52, prolapse in 13, rheumatic fever in 16, coronary disease in eight, congenital disease in nine, and endocarditis in five. Multiple abnormalities were usually present. Four patients had severe calcification of the anulus. A reconstruction was accomplished in almost all patients. A ring annuloplasty was performed in all but two small children, but annuloplasty alone was adequate in only 17 patients. Fifty-eight had resection of 1 to 4 cm of diseased mitral leaflet. In 23 patients, chordal transposition or shortening was employed. Aortic leaflet repair was done in 28. Shortened, fused chordae (one to eight) were divided in 13 patients. Additional procedures performed in 28 patients included coronary bypass in 14. A successful repair was accomplished in all but one patient (moderate residual insufficiency). Two late hospital deaths were unrelated to the mitral repair. Following hospital discharge, ring dehiscence necessitated repeat operation in one patient. Thromboembolism produced a permanent minor neurological deficit in only one patient. There have been no late recurrences of insufficiency. Recurrent endocarditis necessitated valve replacement in three patients. A late Doppler evaluation of 95 patients for mitral insufficiency revealed none in 82, a trace in 12, and moderate insufficiency in one. Late catheterization in 16 patients revealed no insufficiency. The data suggest that reconstruction, rather than prosthetic valve replacement, can be successfully performed in over 90% of patients with nonrheumatic, noncalcified mitral valves. A much wider use of the technique seems strongly indicated.

The effects of amrinone versus dobutamine on myocardial mechanics and energetics after hypothermic global ischemia.

The effects on the postischemic myocardium of amrinone and dobutamine were studied in canine hearts that underwent 90 minutes of hypothermic (10 degrees C) arrested ischemia. In an isolated heart preparation cross-circulated by a support dog, left ventricular pressure-volume loops were collected under a constant afterload based on a mock circulatory system and a range of preload conditions controlled by a computerized servo volume pump. Dobutamine (0, 5, 10, 15 micrograms/kg per minute) and amrinone (0, 0.75, 1.5, 3.0 mg/kg) were tested in this order based on the weights of the support dogs in eight experiments. Changes in intrinsic myocardial contractility were analyzed as percent increases in the preload recruitable stroke work area from baselines. Dobutamine exhibited significant dose-related increases in the preload recruitable stroke work area. Amrinone did not produce significant increases in preload recruitable stroke work area at 0.75 mg/kg; amrinone's inotropic effect was equivalent to dobutamine, 5 micrograms/kg per minute at 1.5 mg/kg, and at the maximum dose (3.0 mg/kg) it was equivalent to dobutamine, 10 micrograms/kg per minute. The myocardial energetic efficiency was determined from the analysis of the myocardial oxygen consumption-pressure volume area relationship. The y intercept represents the basal metabolic oxygen requirement of the unloaded beating heart, and the slope is inversely proportional to the rate of energy conversion for increasing loading conditions. Dobutamine significantly increased the y intercepts, but it had no effects on the slopes. These changes demonstrate reduced myocardial efficiencies that are consistent with previous reports. Amrinone (0.75 and 1.50 mg/kg) did not result in change of the y intercepts and the slopes of myocardial oxygen consumption-pressure-volume area relationship from baseline conditions. The y intercept was increased with amrinone (3.0 mg/kg), although still not significantly higher than baseline and not to the extents of the dobutamine group. Dobutamine did not have any primary effect on coronary resistance, while amrinone significantly reduced coronary resistance in all loading conditions at 1.5 and 3.0 mg/kg. This study demonstrates that the inotropic effects of amrinone tested under this constant afterload preparation were lower than those of dobutamine. Amrinone has a superior profile of myocardial efficiency on the postischemic myocardium since it does not produce the oxygen-wasting effects of the traditional inotropic agents such as the beta agonists. This benefit, together with amrinone's coronary dilating effects, critically improves the supply/demand ratio that may be of importance in certain clinical situations.

Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia.

Cardiopulmonary bypass results in a "euthyroid sick" state. Recently, interest has focused on the relationship between low serum triiodothyronine levels and postoperative cardiovascular hemodynamics. The present study was undertaken to more clearly define the acute effects of triiodothyronine on myocardial mechanics and energetics after hypothermic global ischemia using an ex-vivo canine heart preparation to model the clinical condition. Experiments were performed on isolated hearts subjected to hyperkalemic arrest with 90 minutes of hypothermic (10 degrees C) ischemia. Isolated hearts were cross-perfused by euthyroid support dogs in which triiodothyronine levels spontaneously decreased by 65% to 75% (p < 0.01) after the initiation of cross-perfusion. In nine heart preparations, triiodothyronine (Triostat) was given as a bolus dose (0.2 micrograms/kg) after 1 hour of baseline data collection with a subsequent measurable rise in serum triiodothyronine levels (p < 0.01). In six postischemic hearts, reverse triiodothyronine was given as a 0.2 micrograms/kg bolus. Triiodothyronine was also administered to a group of eight nonischemic, continuously perfused isolated hearts. Intrinsic myocardial contractility was assessed by analysis of the preload recruitable stroke work area, energetic efficiency from the myocardial oxygen consumption-pressure-volume area relationship, and coronary vascular resistance from analysis of coronary flow and perfusion pressure. Acute administration of triiodothyronine to postischemic hearts improved the preload recruitable stroke work area from 9.5 +/- 1.42 to 14.9 +/- 2.03 x 10(7) erg/ml, a 56% increase from baseline (p < 0.001), but had no effect on the preload recruitable stroke work area of the nonischemic hearts. The inotropic response resulting from triiodothyronine treatment did not alter the myocardial oxygen consumption-pressure-volume area relationship. Triiodothyronine treatment was associated with significantly decreased coronary resistance and increased coronary flow through a range of diastolic loading conditions in the postischemic hearts. The biologically inactive thyroid hormone metabolite reverse triiodothyronine was without effect on any of the measured parameters. On the basis of these results, we conclude that the low triiodothyronine state of cardiopulmonary bypass can be reproduced in this isolated heart model and that acute triiodothyronine treatment results in a unique inotropic action manifest only in the postischemic reperfused myocardium and is accomplished without oxygen wasting effects.