Regenerating functional myocardium: improved performance after skeletal myoblast transplantation.

The adult heart lacks reserve cardiocytes and cannot regenerate. Therefore, a large acute myocardial infarction often develops into congestive heart failure. To attempt to prevent this progression, we transplanted skeletal myoblasts into cryoinfarcted myocardium of the same rabbits (autologous transfer), monitored cardiac function in vivo for two to six weeks and examined serial sections of the hearts by light and electron microscopy. Islands of different sizes comprising elongated, striated cells that retained characteristics of both skeletal and cardiac cells were found in the cryoinfarct. In rabbits in which myoblasts were incorporated, myocardial performance was improved. The ability to regenerate functioning muscle after autologous myoblast transplantation could have a important effect on patients after acute myocardial infarction.

Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary beta2-adrenergic receptor gene delivery.

Exogenous gene delivery to alter the function of the heart is a potential novel therapeutic strategy for treatment of cardiovascular diseases such as heart failure (HF). Before gene therapy approaches to alter cardiac function can be realized, efficient and reproducible in vivo gene techniques must be established to efficiently transfer transgenes globally to the myocardium. We have been testing the hypothesis that genetic manipulation of the myocardial beta-adrenergic receptor (beta-AR) system, which is impaired in HF, can enhance cardiac function. We have delivered adenoviral transgenes, including the human beta2-AR (Adeno-beta2AR), to the myocardium of rabbits using an intracoronary approach. Catheter-mediated Adeno-beta2AR delivery produced diffuse multichamber myocardial expression, peaking 1 week after gene transfer. A total of 5 x 10(11) viral particles of Adeno-beta2AR reproducibly produced 5- to 10-fold beta-AR overexpression in the heart, which, at 7 and 21 days after delivery, resulted in increased in vivo hemodynamic function compared with control rabbits that received an empty adenovirus. Several physiological parameters, including dP/dtmax as a measure of contractility, were significantly enhanced basally and showed increased responsiveness to the beta-agonist isoproterenol. Our results demonstrate that global myocardial in vivo gene delivery is possible and that genetic manipulation of beta-AR density can result in enhanced cardiac performance. Thus, replacement of lost receptors seen in HF may represent novel inotropic therapy.

In vivo ventricular gene delivery of a beta-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction.

BACKGROUND: Genetic manipulation to reverse molecular abnormalities associated with dysfunctional myocardium may provide novel treatment. This study aimed to determine the feasibility and functional consequences of in vivo beta-adrenergic receptor kinase (betaARK1) inhibition in a model of chronic left ventricular (LV) dysfunction after myocardial infarction (MI). METHODS AND RESULTS: Rabbits underwent ligation of the left circumflex (LCx) marginal artery and implantation of sonomicrometric crystals. Baseline cardiac physiology was studied 3 weeks after MI; 5x10(11) viral particles of adenovirus was percutaneously delivered through the LCx. Animals received transgenes encoding a peptide inhibitor of betaARK1 (Adeno-betaARKct) or an empty virus (EV) as control. One week after gene delivery, global LV and regional systolic function were measured again to assess gene treatment. Adeno-betaARKct delivery to the failing heart through the LCx resulted in chamber-specific expression of the betaARKct. Baseline in vivo LV systolic performance was improved in Adeno-betaARKct-treated animals compared with their individual pre-gene delivery values and compared with EV-treated rabbits. Total beta-AR density and betaARK1 levels were unchanged between treatment groups; however, beta-AR-stimulated adenylyl cyclase activity in the LV was significantly higher in Adeno-betaARKct-treated rabbits compared with EV-treated animals. CONCLUSIONS: In vivo delivery of Adeno-betaARKct is feasible in the infarcted/failing heart by coronary catheterization; expression of betaARKct results in marked reversal of ventricular dysfunction. Thus, inhibition of betaARK1 provides a novel treatment strategy for improving the cardiac performance of the post-MI heart.

Intracoronary adenovirus-mediated delivery and overexpression of the beta(2)-adrenergic receptor in the heart : prospects for molecular ventricular assistance.

BACKGROUND: Genetic modulation of ventricular function may offer a novel therapeutic strategy for patients with congestive heart failure. Myocardial overexpression of beta(2)-adrenergic receptors (beta(2)ARs) has been shown to enhance contractility in transgenic mice and reverse signaling abnormalities found in failing cardiomyocytes in culture. In this study, we sought to determine the feasibility and in vivo consequences of delivering an adenovirus containing the human beta(2)AR cDNA to ventricular myocardium via catheter-mediated subselective intracoronary delivery. METHODS AND RESULTS: Rabbits underwent percutaneous subselective catheterization of either the left or right coronary artery and infusion of adenoviral vectors containing either a marker transgene (Adeno-betaGal) or the beta(2)AR (Adeno-beta(2)AR). Ventricular function was assessed before catheterization and 3 to 6 days after gene delivery. Both left circumflex- and right coronary artery-mediated delivery of Adeno-beta(2)AR resulted in approximately 10-fold overexpression in a chamber-specific manner. Delivery of Adeno-betaGal did not alter in vivo left ventricular (LV) systolic function, whereas overexpression of beta(2)ARs in the LV improved global LV contractility, as measured by dP/dt(max), at baseline and in response to isoproterenol at both 3 and 6 days after gene delivery. CONCLUSIONS: Percutaneous adenovirus-mediated intracoronary delivery of a potentially therapeutic transgene is feasible, and acute global LV function can be enhanced by LV-specific overexpression of the beta(2)AR. Thus, genetic modulation to enhance the function of the heart may represent a novel therapeutic strategy for congestive heart failure and can be viewed as molecular ventricular assistance.

Mechanical correlates of the third heart sound.

In seven chronically instrumented conscious dogs, micromanometers measured left ventricular pressure, and ultrasonic dimension transducers measured left ventricular minor-axis diameter; the latter recording was filtered to examine data between 20 and 100 Hz. Acceptable external heart sounds were recorded with a phonocardiographic microphone in four of the seven dogs. With each dog sedated, intubated and mechanically ventilated, data were obtained during hemodynamic alterations produced by volume loading, phenylephrine, calcium infusion and vena caval occlusion. Damped oscillations were noted consistently in the left ventricular diameter waveform toward the end of rapid ventricular filling. These wall vibrations, assessed by the filtered diameter, correlated well with the third heart sound (S3) on the phonocardiogram. The peak frequency of the wall vibrations increased with increased diastolic pressure (p = 0.004), probably reflecting an increase in myocardial wall stiffness. In contrast, the amplitude of the vibrations varied directly with left ventricular filling rate (p = 0.0001). Thus, S3 seemed to be related specifically to ventricular wall vibrations during rapid filling, and the spectra of the amplitude-frequency relation shifted toward the audible range with increases in diastolic pressure, wall stiffness or filling rate. Spectral analysis of S3 may be useful in assessing pathologic changes in myocardial wall properties.

Early postoperative changes in regional systolic and diastolic left ventricular function after transmyocardial laser revascularization: a comparison of holmium:YAG and CO2 lasers.

OBJECTIVES: The purpose of this study was to determine the short-term effects of transmyocardial laser revascularization (TMR) on regional left ventricular systolic and diastolic function, myocardial blood flow (MBF) and myocardial water content (MWC). BACKGROUND: Clinical studies of TMR have noted a significant incidence of cardiac complications in the early postoperative period. However, the early post-treatment effects of laser therapy on the myocardium and their potential contribution to postoperative cardiac morbidity are unknown. METHODS: Swine underwent holmium:yttrium-aluminum-garnet (holmium:YAG) (n = 12) or carbon dioxide (CO2) (n = 12) laser TMR. Regional systolic function for the lased and nonlased regions was quantitated using preload recruitable work area (PRWA) and regional diastolic function with the ventricular stiffness constant alpha. RESULTS: Preload recruitable work area was significantly decreased in the lased regions both 1 (59.8+/-13.0% of baseline, p = 0.02) and 6 h (64.2+/-9.4% of baseline, p = 0.02) after holmium:YAG TMR. This decreased PRWA was associated with a significant reduction in MBF to the lased regions (13.2% reduction at 1 h, p = 0.02; 18.4% decrease at 6 h post-TMR, p = 0.01). These changes were not seen after CO2 laser TMR. A significant increase in MWC (1.4+/-0.3% increase with holmium:YAG, p = 0.004; 1+/-0.2% increase with CO2, p = 0.002) and alpha (217.4+/-44.2% of baseline 6 h post-holmium:YAG TMR, p = 0.05; 206+/-36.7% of baseline 6 h post-CO2 TMR, p = 0.03) was seen after TMR with both lasers. CONCLUSIONS: In the early postoperative setting, impaired regional systolic function in association with regional ischemia is seen after TMR with a holmium:YAG laser. Both holmium:YAG and CO2 lasers are associated with increased MWC and impaired diastolic relaxation in the lased regions. These changes may explain the significant incidence of early postoperative cardiac morbidity. The impact of these findings on anginal relief and long-term outcome are not known.

Dissociation between early recovery of regional function and purine nucleotide content in postischaemic myocardium in the conscious dog.

Since abnormalities in regional myocardial function and nucleotide metabolism persist for a prolonged period after a brief coronary occlusion the temporal relation between the resolution of myocardial dysfunction and repletion of nucleotide pools in postischaemic myocardium was studied in conscious mildly sedated animals. In a second experiment 5-amino-4-imidazolecarboxamide riboside (AICAriboside) was infused in an attempt to influence myocardial function by altering the rate of adenine nucleotide synthesis. Conscious dogs mildly sedated with morphine underwent coronary occlusion for 15 min followed by reperfusion for 30 min or 12 h, at which time a myocardial sample was obtained for nucleotide analysis. Segment shortening averaged 62% of control values at 15 min of reperfusion and increased to 81% of control by 12 h of reperfusion (p less than 0.05). Adenine nucleotide content was 75(5)% of control after 30 min of reperfusion and did not change significantly over the next 12 h of reperfusion. Thus the early return of systolic function was not accompanied by a detectable increase in total adenine nucleotide content. In the second experiment a pronounced stimulation of the proximal purine nucleotide synthetic pathway occurred as evidenced by a 13-fold to 25-fold increase in inosine monophosphate content. One branch of the distal purine pathway was also stimulated as evidenced by complete repletion of guanine nucleotide pools, but the product of the other branch (adenine nucleotides) did not increase significantly. These results indicate a selective limitation of the distal adenine nucleotide synthetic pathway in postischaemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Performance status and outcome after coronary artery bypass grafting in persons aged 80 to 93 years.

Although coronary artery bypass grafting (CABG) effectively eliminates or diminishes symptoms of myocardial ischemia, the overall performance status and functional outcome in elderly patients undergoing CABG is poorly documented. Therefore, 86 consecutive patients aged 80 to 93 years undergoing isolated CABG were reviewed. Preoperative, intraoperative, and postoperative characteristics and pre- and postoperative performance status (Karnofsky score) were examined. Forty patients (47%) were women, and most patients had highly symptomatic coronary artery disease with class III or IV angina in 94% and unstable angina in 90%. Significant co-morbid disease was present in 49% of patients, and cardiac catheterization revealed left main or 3-vessel disease in 74% of patients. The rate of significant in-hospital complications was 29%, with infection in 14%, stroke in 9%, and respiratory failure in 8% being most frequent. Median performance status (Karnofsky score) improved from 20 to 70% (p = 0.0001) with 89% of hospital survivors being discharged home. Factors associated with failure to achieve a successful functional outcome at discharge were presence of 1 or more preoperative co-morbid conditions (p = 0.048), preoperative myocardial infarction within 7 days of operation (p less than 0.01), and postoperative low cardiac output (p less than 0.01). Survival at 30 days, 6 months, and 3 years were 90, 78, and 64%, respectively. These data demonstrate that CABG can be offered to selected elderly patients with acceptable morbidity and mortality, marked improvement in performance status, and an acceptable quality of life.

The effects of dopamine on myocardial functional recovery after reversible ischemic injury.

Dopamine frequently is used to improve cardiac performance after acute myocardial ischemia. Inotropic agents, however, increase myocardial oxygen demand and could potentially delay recovery from ischemic injury. To evaluate this problem, we studied eight chronically instrumented dogs in the conscious state and performed two 15-minute coronary occlusions 48 hours apart. After one of the occlusions, either dopamine (15 micrograms/kg/min) or saline placebo was administered intravenously from 1.0 to 1.5 hours of reperfusion. The alternative infusion was given during the second study. Preload recruitable work area, the area beneath the stroke work versus end-diastolic length relationship, was used to assess intrinsic myocardial performance. Ischemia decreased preload recruitable work area to 13% of control after both occlusions. After reperfusion, a 30-minute dopamine infusion acutely increased myocardial function nearly threefold as compared with placebo. Myocardial performance after dopamine administration, however, was significantly depressed compared with placebo throughout the remaining 24 hours of reperfusion (p less than 0.01). These data indicate that dopamine may impair functional recovery after ischemic myocardial injury and suggest that inotropic interventions should be used in this setting only when absolutely indicated.

Evaluation of suture techniques for mitral valve replacement.

Although periprosthetic leak is presently uncommon after mitral valve replacement, suture line disruption still occurs and may be significant in some patients. Suture technique is obviously an important factor in preventing disruption, but few authors have examined this variable. The purpose of this study was to determine which of four suture methods for mitral valve replacement maximized prosthetic stability in the mitral anulus. Horizontal mattress sutures with subannular pledgets, horizontal mattress sutures with supra-annular pledgets, figure-of-eight sutures, and interrupted simple sutures were compared. A Carpentier-Edwards sewing ring was sutured to the mitral anulus of intact canine left ventricles, each technique randomly assigned to eight hearts. Suture size, number of bites, and annular depth were maintained constant in all groups. Progressively increasing force was applied across the suture line until disruption occurred. The yield force at initial suture disruption was measured by a semiconductor strain-gauge transducer and defined the experimental end point. Subannular pledget-supported sutures required the greatest force (38.4 +/- 0.8 N) to produce prosthetic dehiscence and were significantly more secure than supra-annular pledgets (32.7 +/- 0.5 N). The two suture techniques in which pledgets were used were better than the nonsupported sutures, the mean yield force averaging 28.3 +/- 0.3 N for figure-of-eight and 21.3 +/- 0.7 N for interrupted simple sutures. Although clinical techniques may vary with prosthetic valve design, surgical preference, or pathological anatomy, this study suggests that horizontal mattress sutures with subannular pledgets provide the best prosthetic valve stability during mitral valve replacement.

A physiologic comparison of external cardiac massage techniques.

On the basis of recent investigation, controversy has arisen regarding which of several cardiopulmonary resuscitation methods optimizes hemodynamics. The present study was designed to compare five recently described chest compression techniques: high-impulse manual chest compression at 150/min, mechanical compression at 60/min with simultaneous ventilation, mechanical compression at 60/min with simultaneous ventilation and either systolic or diastolic abdominal compression, and pneumatic vest compression at 60/min. Eight dogs were chronically instrumented with electromagnetic flow probes in the ascending and descending aorta while matched micromanometers measured aortic, left ventricular, and pleural pressures. At study, each dog was anesthetized with morphine, intubated, and the heart was fibrillated by rapid ventricular pacing. The five cardiopulmonary resuscitation methods were performed randomly in each preparation within 7 to 10 minutes of arrest. In four dogs, brachiocephalic blood flow was computed as total cardiac output minus descending aortic blood flow, and in all dogs coronary perfusion pressure was calculated as mean diastolic aortic pressure minus mean diastolic left ventricular pressure. Average cardiac output for seven studies was 662 +/- 61 ml/min with high-impulse manual compression, 340 +/- 46 ml/min with mechanical compression and simultaneous ventilation, 336 +/- 45 ml/min with mechanical compression and simultaneous ventilation with systolic abdominal compression, 366 +/- 52 ml/min with mechanical compression and simultaneous ventilation with diastolic abdominal compression, and 196 +/- 29 ml/min with vest resuscitation (high-impulse manual compression significantly greater than other techniques by multivariate analysis, p less than 0.05). Brachiocephalic blood flow generally followed cardiac output and was statistically the greatest with high-impulse manual compression at 273 +/- 47 ml/min (p less than 0.05). Finally, high-impulse manual compression provided the highest coronary perfusion pressure of 31 +/- 4 mm Hg (p less than 0.05) compared to 23 +/- 2 mm Hg for mechanical compression and simultaneous ventilation, 23 +/- 2 mm Hg for mechanical compression and simultaneous ventilation with systolic abdominal compression, 23 +/- 3 mm Hg for mechanical compression and simultaneous ventilation with diastolic abdominal compression, and 11 +/- 2 mm Hg for vest resuscitation. These data demonstrate that high-impulse manual compression generated physiologically and statistically superior hemodynamics when compared with other methods in this model of cardiopulmonary resuscitation.

Physiologic determinants of coronary blood flow during external cardiac massage.

Adequate coronary blood flow is a major determinant for successful resuscitation from cardiopulmonary arrest. To develop compression techniques that optimize coronary blood flow, we implanted in eight dogs electromagnetic flow probes that measured circumflex coronary blood flow and ascending aortic blood flow. Micromanometers measured left ventricular and aortic pressures. Each dog was anesthetized and intubated, and the heart was fibrillated electrically. High-impulse manual chest compressions were performed with the dog in the supine position, and compression rate was varied from 60/min to 150/min. Antegrade coronary blood flow occurred primarily during artificial diastole, and there was a brief period of retrograde coronary blood flow with compression during artificial systole. Cardiac output and diastolic aortic pressure increased with compression rate, significantly augmenting peak coronary blood flow velocity. However, diastolic perfusion time decreased linearly with compression rate and limited coronary perfusion at rates greater than 120/min. As a result, net coronary blood flow during high-impulse manual chest compression was determined primarily by diastolic aortic pressure and diastolic perfusion time. Coronary blood flow was optimized in this model at a compression rate of 120/min.

Comparison of survival after mitral valve replacement with biologic and mechanical valves in 1139 patients.

OBJECTIVE: We sought to compare 10-year survival in patients after mitral valve replacement with biologic or mechanical valve prostheses. METHODS: Retrospective survival analysis was performed on data from 1139 consecutive patients older than 18 years of age undergoing mitral valve replacement with Carpentier-Edwards (n = 495; Baxter Healthcare Corp, Irvine, Calif) or St Jude Medical (n = 644; St Jude Medical, Inc, St Paul, Minn) prostheses. RESULTS: The 10-year survival was not statistically different between the patients receiving Carpentier-Edwards valves and those receiving St Jude Medical valves (P =.16). Adjusted survival estimates at 2, 5, and 10 years were 82% +/- 2% (95% confidence intervals, 79%-85%), 69% +/- 2% (95% confidence intervals, 64%-73%), and 42% +/- 3% (95% confidence intervals, 37%-48%), respectively, for the Carpentier-Edwards group and 83% +/- 2% (95% confidence intervals, 80%-86%), 72% +/- 2% (95% confidence intervals, 69%-76%), and 51% +/- 3% (95% confidence intervals, 45%-58%), respectively, for the St Jude Medical group. Predictors of worse survival after mitral valve replacement are older age, lower ejection fraction, presence of class IV congestive heart failure, coronary artery disease, renal disease, smoking history, hypertension, concurrent other valve surgery, and redo heart surgery. CONCLUSION: Choice of biologic or mechanical prosthesis does not significantly affect long-term patient survival after mitral valve replacement.

Early effects of right ventricular volume overload on ventricular performance and beta-adrenergic signaling.

OBJECTIVE: Right ventricular dysfunction is a poorly understood but persistent clinical problem. This study was undertaken to evaluate ventricular performance and beta-adrenergic receptor signaling in a tricuspid regurgitation model of right ventricular overload. METHODS: Seventeen dogs were chronically instrumented with epicardial dimension transducers. By means of the shell-subtraction model, right ventricular pressure-volume relationships were evaluated in normal and right ventricular overload states. Right ventricular chamber performance was quantified by the stroke work at an end-diastolic volume relationship. RESULTS: Right ventricular volume overload caused a 28% +/- 11% and 31% +/- 9% decline in chamber performance acutely and at 1 week, respectively, whereas end-diastolic volume increased from 45 +/- 21 to 60 +/- 30 mL (P =. 019). beta-Adrenergic receptor signaling in myocardial samples was assessed, examining adenylyl cyclase and G-protein-coupled receptor kinase activity. Stimulated adenylyl cyclase activity significantly decreased, and G-protein-coupled receptor kinase activity significantly increased in both left and right ventricular samples caused by increased levels of beta-adrenergic receptor kinase 1. No change in beta-adrenergic receptor density was seen at 1 week. CONCLUSIONS: Early right ventricular overload is associated with impaired right ventricular chamber contractility, dilation, and, importantly, a biventricular alteration of beta-adrenergic receptor signaling.

Left ventricular adaptation to aortic regurgitation in conscious dogs.

OBJECTIVE: Cardiac failure as a result of valvular heart disease remains a major clinical problem that frequently leads to ventricular dysfunction, myocardial failure, and even death. The development of irreversible myocardial damage may be especially insidious in volume overload as a result of aortic or mitral regurgitation. METHODS AND RESULTS: Left ventricular wall volume, ventricular function, and myocardial performance were assessed in 10 chronically instrumented conscious dogs before and after creation of aortic regurgitation. Left ventricular wall volume was measured by serial echocardiography. Left ventricular function was assessed by total cardiac output, stroke work, the slope of the Frank-Starling relationship, and the slope of the end-systolic pressure-volume relationship. Myocardial performance was assessed by the slope of the myocardial power output versus end-diastolic strain relationship. End-diastolic wall stress and volume both increased acutely and remained elevated after creation of aortic regurgitation. Peak systolic wall stress increased initially (1 to 3 weeks) from 336 +/- 30 to 369 +/- 55 mm Hg but returned to control values as left ventricular wall volume increased from 78 +/- 13 to 88 +/- 16 ml after development of compensatory hypertrophy. Left ventricular systolic function remained constant or increased and was maintained initially by increased myocardial performance, which returned to baseline levels after the development of compensatory hypertrophy. CONCLUSIONS: Myocardial performance and ventricular function vary independently in aortic regurgitation. Measures of myocardial performance such as the myocardial power output versus end-diastolic strain relationship may be useful in clinical assessment of aortic regurgitation.

Ex vivo adenovirus-mediated gene transfer to the adult rat heart.

OBJECTIVE: The ability to transfer genes to adult myocardium may have therapeutic implications for cardiac transplantation. We investigated the feasibility of adenovirus-mediated transfer of marker genes LacZ and Luciferase, as well as the potentially therapeutic gene of the human beta2-adrenergic receptor in a rat heterotopic heart transplant model. METHODS: Donor hearts were flushed with 10(12) total viral particles of one of three transgenes. Hearts were harvested at various time points after transplantation. LacZ-treated hearts were assessed by histologic staining and Luciferase-treated hearts were assayed for specific luminescence activity. Hearts treated with beta2-adrenergic receptor underwent radioligand binding assays and immunohistochemistry with the use of an antibody specific for the human beta2-adrenergic receptor. RESULTS: LacZ hearts revealed diffuse myocyte staining as opposed to none within controls at 5 days. Luciferase hearts demonstrated a mean activity of 970,000 +/- 220,000 arbitrary light units versus 500 +/- 200 for the controls (p = 0.001). Total beta2-adrenergic receptor densities (fmol/mg membrane protein) for hearts that received the beta2-adrenergic receptor transgene at 3, 5, 7, 10, and 14 days after infection were as follows: right ventricle, 488.5 +/- 126.8, 519.4 +/- 81.8,* 477.1 +/- 51.8,* 183.0 +/- 6.5,* and 82.7 +/- 19.1; left ventricle, 511.0 +/- 167.6, 1206.4 +/- 321.8,* 525.3 +/- 188.7, 183.5 +/- 18.6,* and 75.9 +/- 15.2 (*p < 0.05 vs control value of 75.6 +/- 6.4). Immunohistochemical analysis revealed diffuse staining of varying intensity within myocardial sarcolemmal membranes. CONCLUSIONS: We conclude that global overexpression of different transgenes is possible during cardiac transplantation and, ultimately, adenovirus-mediated gene transfer may provide a unique opportunity for genetic manipulation of the donor organ, potentially enhancing its function.

Determinants of reoperation after 960 valve replacements with Carpentier-Edwards prostheses.

During the period of 1977 to 1990, 960 Carpentier-Edwards standard prostheses (Baxter Healthcare Corp., Santa Ana, Calif.) were placed in 875 operations. Freedom from reoperation at 10 years was 57% +/- 4%, 76% +/- 3%, and 95% +/- 5% for mitral, aortic, and tricuspid valve replacement, respectively. Age was the only independent determinant of reoperation for both aortic and mitral valves. Likelihood of reoperation decreased with age, with freedom from reoperation after 10 years in patients aged less than 60 years versus 60 or more years being 65% +/- 5% versus 90% +/- 4% after aortic valve replacement and 48% +/- 5% versus 75% +/- 6% after mitral valve replacement. For mitral valve replacement, larger valve size made reoperation more likely, with freedom from reoperation at 10 years being 71% +/- 6% for sizes median less than 31 mm and 57% +/- 5% for sizes 31 mm or larger. For aortic valve replacement, prior median sternotomy reduced freedom from reoperation at 10 years from 80% +/- 3% to 25% +/- 5%. The low prevalence of reoperation affirms the suitability of the Carpentier-Edwards prosthesis for selected elderly patients and for tricuspid valve replacement. Because of their influence on the probability of reoperation, valve size and prior cardiac procedures also merit consideration in the choice of valvular prosthesis.

Calcitonin gene-related peptide enhances the recovery of contractile function in stunned myocardium.

INTRODUCTION: Calcitonin gene-related peptide, a potent vasodilating inotropic agent, increases coronary artery perfusion when administered exogenously and reduces ischemic injury in nonmyocardial tissue. However, it is unclear whether this agent improves recovery of myocardial performance after reversible myocardial ischemia. METHODS: Nine dogs underwent complete occlusion of the left anterior descending coronary artery for 15 minutes and were monitored during 24 hours of reperfusion. Calcitonin gene-related peptide (0.07 microgram. kg(-1). min(-1)), nitroglycerin (65 microgram. kg(-1). min(-1)), or saline solution placebo was infused intravenously during initial reperfusion. Ischemia/reperfusion was repeated in concurrent 24-hour periods until all animals received infusions in random order. Micromanometry and sonomicrometry determined left ventricular pressure and myocardial segment length. Myocardial performance, based on the linear relationship between stroke work and end-diastolic segment length, was estimated with the preload recruitable work area. Results were analyzed as percent control and compared statistically with the use of repeated measures analysis of variance. RESULTS: Recovery of myocardial performance was augmented during reperfusion with calcitonin gene-related peptide infusion relative to placebo

In-hospital and long-term outcome after porcine tricuspid valve replacement.

Porcine bioprostheses are often used for tricuspid valve replacement, yet the long-term outcome after this procedure is not well documented. Therefore, the records of 129 patients undergoing tricuspid valve replacement with Carpentier-Edwards (n = 88) or Hancock (n = 41) prostheses between 1975 and 1993 were reviewed. The operation required a repeat median sternotomy in 66 of 129 (51%) patients, whereas 67 of 129 (52%) underwent double or triple valve replacement. Operative mortality was 14% (2/14) in patients undergoing first-time isolated tricuspid valve replacement and 27% (35/129) overall. Survival at 5, 10, and 14 years was 56% +/- 5%, 48% +/- 5%, and 31% +/- 9%, and freedom from tricuspid reoperation at 5, 10, and 14 years was 96% +/- 3%, 93% +/- 4%, and 49% +/- 17%. No valve thrombosis was observed. In this largest reported series of porcine bioprostheses in the tricuspid position, long-term freedom from valve-related events was excellent because of a low incidence of valve thrombosis and a valve durability of 13 to 15 years in a population with limited life expectancy.

Long-term outcome after biologic versus mechanical aortic valve replacement in 841 patients.

OBJECTIVE: The purpose of this study was to optimize selection criteria of biologic versus mechanical valve prostheses for aortic valve replacement. METHODS: Retrospective analysis was performed for 841 patients undergoing isolated, first-time aortic valve replacement with Carpentier-Edwards (n = 429) or St Jude Medical (n = 412) prostheses. RESULTS: Patients with Carpentier-Edwards and St Jude Medical valves had similar characteristics. Ten-year survival was similar in each group (Carpentier-Edwards 54% 3% versus St Jude Medical 50% 6%; P =.4). Independent predictors of worse survival were older age, renal or lung disease, ejection fraction less than 40%, diabetes, and coronary disease. Carpentier-Edwards versus St Jude Medical prostheses did not affect survival (P =.4). Independent predictors of aortic valve reoperation were younger age and Carpentier-Edwards prosthesis. The linearized rates of thromboembolism were similar, but the linearized rate of hemorrhage was lower with Carpentier-Edwards prostheses (P <.01). Perivalvular leak within 6 months of operation was more likely with St Jude Medical than with Carpentier-Edwards prostheses (P =.02). Estimated 10-year survival free from valve-related morbidity was better for the St Jude Medical valve in patients aged less than 65 years and was better for the Carpentier-Edwards valve in patients aged more than 65 years. Patients with renal disease, lung disease (in patients more than age 60 years), ejection fraction less than 40%, or coronary disease had a life expectancy of less than 10 years. CONCLUSIONS: For first-time, isolated aortic valve replacement, mechanical prostheses should be considered in patients under age 65 years with a life expectancy of at least 10 years. Bioprostheses should be considered in patients over age 65 years or with lung disease (in patients over age 60 years), renal disease, coronary disease, ejection fraction less than 40%, or a life expectancy less than 10 years.