The future direction of the adult heart allocation system in the United States.

Ensuring equitable and fair organ allocation is a central charge of the United Network for Organ Sharing (UNOS) as the Organ Procurement and Transplantation Network (OPTN) through its contract with the Department of Health and Human Services (DHHS). The OPTN/UNOS Board initiated a reassessment of the current allocation system. This paper describes the efforts of the OPTN/UNOS Heart Subcommittee, acting on behalf of the OPTN/UNOS Thoracic Organ Transplantation Committee, to modify the current allocation system. The Subcommittee assessed the limitations of the current three-tiered system, outcomes of patients with status exceptions, emerging ventricular assist device (VAD) population, options for improved geographic sharing and status of potentially disenfranchised groups. They analyzed waiting list and posttransplant mortality rates of a contemporary cohort of patient groups at risk, in collaboration with the Scientific Registry of Transplant Recipients to develop a proposed multi-tiered allocation scheme. This proposal provides a framework for simulation modeling to project whether candidates would have better waitlist survival in the revised allocation system, and whether posttransplant survival would remain stable. The tiers are subject to change, based on further analysis by the Heart Subcommittee and will lead to the development of a more effective and equitable heart allocation system.

Human SERCA2a levels correlate inversely with age in senescent human myocardium.

OBJECTIVES: This study sought to characterize functional impairment after simulated ischemia-reperfusion (I/R) or Ca2+ bolus in senescent human myocardium and to determine if age-related alterations in myocardial concentrations of SERCA2a, phospholamban, or calsequestrin participate in senescent myocardial dysfunction. BACKGROUND: Candidates for elective cardiac interventions are aging, and an association between age and impairment of relaxation has been reported in experimental animals. Function of the sarcoplasmic reticulum resulting in diastolic dysfunction could be dysregulated at the level of cytosolic Ca2+ uptake by SERCA2a, its inhibitory subunit (phospholamban), or at the level of Ca2+ binding by calsequestrin. METHODS: Human atrial trabeculae from 17 patients (45-75 years old) were suspended in organ baths, field simulated at 1 Hz, and force development was recorded during I/R (45/120 min). Trabeculae from an additional 12 patients (53-73 years old) were exposed to Ca2+ bolus (2-3 mmol/L bath concentration). Maximum +/- dF/dt and the time constant of force decay (tau) were measured before and after I/R or Ca2+ bolus and related to age. SERCA2a, phospholamban, and calsequestrin from 12 patients (39-77 years old) were assessed by immunoblot. RESULTS: Functional results indicated that maximum +/-dF/dt and tau were prolonged in senescent (>60 years) human myocardium after I/R (p < 0.05). Calcium bolus increased the maximum +/-dF/dt and decreased tau in younger, but not older patients (p < 0.05). SERCA2a and the ratio of SERCA2a to either phospholamban or calsequestrin were decreased in senescent human myocardium (p < 0.05). CONCLUSIONS: Senescent human myocardium exhibits decreased myocardial SERCA2a content with age, which may, in part, explain impaired myocardial function after either I/R or Ca2+ exposure.

Vinblastine attenuates endotoxin-induced impairment of CGMP-mediated pulmonary vasorelaxation.

We tested the hypothesis that neutrophils contribute to endotoxin-induced impairment of endothelium-dependent and -independent cyclic guanosine monophosphate (cGMP)-mediated pulmonary vascular smooth muscle relaxation. Rats were studied 6 h after endotoxin (20 mg/kg, intraperitoneal) or saline (1 cc, intraperitoneal). Neutrophil-depleted rats were studied 4 days after administration of vinblastine (750 micrograms/kg, intravenous). Concentration-response curves were generated for acetylcholine and sodium nitroprusside in isolated pulmonary arterial rings (10(-9) M to 10(-6) M). The absolute neutrophil count of controls was 1050 +/- 206 neutrophils/mL, and the absolute neutrophil count of vinblastine-treated rats was 100 +/- 41 neutrophils/mL (p < .05 versus controls) and 25 +/- 25 neutrophils/mL in vinblastine-treated rats receiving endotoxin (p < .05 versus control and endotoxin). Endotoxin-induced impairment of endothelium-dependent and -independent cGMP-mediated pulmonary vasorelaxation was significantly attenuated by prior treatment with vinblastine. We conclude that neutrophils contribute to the pathogenesis of endotoxin-induced impairment of cGMP-mediated pulmonary vascular smooth muscle relaxation.

Constructive priming of myocardium against ischemia-reperfusion injury.

Ischemia and ischemic stress hormones induce endogenous cardiac protection against ischemia-reperfusion (I/R) injury. Although ischemia and ischemic stress hormones are accompanied by increased [Ca2+], it is unknown whether either opening of the sarcoplasmic reticular ryanodine Ca2+ channel (SR RyR) or inhibition of Ca2+ uptake by the sarcoendoplasmic reticular Ca(2+)-ATPase (SERCA) prior to I/R can similarly induce post-I/R functional protection. To study this, isolated, crystalloid perfused Sprague-Dawley rat hearts were used to assess the effects of inducing a pre-ischemic [Ca2+]i load by either priming the SR RyR with ryanodine (Ry, 5 nM/2 min) or by transient blockade of the SERCA 10 min prior to global I/R (20 min). A pre-ischemic Ca2+ load by either SR RyR activation or SERCA blockade improved post-ischemic myocardial functional recovery (developed pressure, end diastolic pressure, coronary flow, heart rate, and left ventricular creatine kinase activity). We conclude that 1) Ca(2+)-induced myocardial functional protection involves the SR Ca2+ source, 2) a pre-ischemic Ca2+ load induced with either Ry or thapsigargin constructively primes against myocardial I/R injury, and 3) Ca(2+)-induced cardioadaptation to I/R injury may have important therapeutic implications prior to planned ischemic events such as cardiac allograft preservation and cardiac bypass surgery.

Fatal air embolism to the right side of the heart during pneumonectomy for carcinoma. Result of broncho-azygous vein communication and positive-pressure ventilation.

A 59-year-old white man had an extensive bronchogenic carcinoma of the right upper lobe. During the course of pneumonectomy, the patient died unexpectedly. At autopsy, massive right-sided air embolism was evident, associated with broncho-azygous vein communication. The cause of the air embolism and subsequent death was almost certainly related to positive-pressure ventilation, allowing entry of air into the systemic venous system through the broncho-azygous vein communication. Because of the clinical implications of this problem, the case is reported, and suggestions for management are offered.

Successful management of massive pulmonary embolism occurring during cardiopulmonary bypass for mitral valve replacement.

Massive pulmonary embolism occurred during cardiopulmonary bypass in a patient requiring mitral valve replacement. Successful management of this unusual problem is described.

Pulmonary resection for multi-drug resistant tuberculosis.

OBJECTIVES: Mycobacterium tuberculosis continues to be a major cause of morbidity and mortality throughout the world. Complacency by the medical profession and by patients has caused a new strain of Mycobacterium tuberculosis to emerge that is highly resistant to current antibiotics. The possibility of a new worldwide epidemic of drug-resistant Mycobacterium tuberculosis is of concern. Optimal therapy for patients infected with multi-drug resistant tuberculosis often requires surgical intervention to eradicate the infection. We report on our experience with pulmonary resection for multi-drug resistant tuberculosis. METHODS: During a 17-year period, 172 patients underwent 180 pulmonary resections. All patients had multi-drug resistant tuberculosis and had a minimum of 3 months of medical therapy before surgery. Muscle flaps were frequently used to avoid residual space and bronchial stump problems. RESULTS: During the study period, 98 lobectomies and 82 pneumonectomies were performed. Eight patients underwent multiple procedures. Operative mortality was 3.3% (6/180). Three patients died of respiratory failure, 2 patients died of a cerebrovascular accident, and 1 patient had a myocardial infarction. Late mortality was 6.8% (11/166). Significant morbidity was 12% (20/166). One half (91) of the patients had positive sputum at the time of surgery. After the operation, the sputum remained positive in only 4 (2%) patients. Mean length of follow-up was 7.6 years (range 4-204 months). CONCLUSIONS: Surgery remains an important adjunct to medical therapy for the treatment of multi-drug resistant Mycobacterium tuberculosis. In the setting of localized disease, persistent sputum positivity, or patient intolerance of medical therapy, pulmonary resection should be undertaken. Pulmonary resection for multi-drug resistant tuberculosis can be performed with acceptable operative morbidity and mortality.

Cardiac preconditioning with calcium: clinically accessible myocardial protection.

Cardiac preconditioning is mediated by protein kinase C. Although endogenous calcium is a potent stimulus of protein kinase C, it remains unknown whether preischemic administration of exogenous calcium can induce protein kinase C-mediated myocardial protection against ischemia-reperfusion injury. To study this, calcium chloride was administered retrogradely through the aorta at a rate 5 nmol/min for 2 minutes to isolated perfused rat hearts 10 minutes before a 20-minute ischemia and 40-minute reperfusion insult. Calcium-mediated cardioadaptation was then linked to protein kinase C by means of the protein kinase C inhibitor chelerythrine (20 mumol.L-1.2 min-1). To determine whether exogenous calcium administration induces protein kinase C translocation and activation, immunohistochemical staining for the calcium-dependent protein kinase C isoform alpha was performed on adjacent 5 microns myocardial sections with and without calcium chloride treatment. Results indicated that preischemic calcium chloride administration improved myocardial functional recovery, as determined by enhanced developed pressure, improved coronary flow, reduced end-diastolic pressure, and decreased creatine kinase leakage during reperfusion. Beneficial effects of calcium chloride were eliminated by concurrent protein kinase C inhibition. Immunohistochemical staining for the alpha isoform of protein kinase C demonstrated that calcium chloride induces translocation of this isoform from the cytoplasm to the sarcolemma, indicating that exogenous calcium administration activates this isoform. These results suggest that calcium chloride, a safe and routinely administered agent, can induce protein kinase C-mediated cardiac preconditioning. Calcium-induced cardioadaptation to ischemia-reperfusion injury may be promising as a clinically feasible therapy before planned ischemic events such as cardiac allograft preservation and elective cardiac operations.

Hydrogen peroxide induces tumor necrosis factor alpha-mediated cardiac injury by a P38 mitogen-activated protein kinase-dependent mechanism.

BACKGROUND: Oxidant stress caused by ischemia or endotoxemia induces myocardial dysfunction and cardiomyocyte death; however, mechanisms responsible remain unknown. We hypothesized that hydrogen peroxide (H2O2) induces myocardial dysfunction and cardiomyocyte death via P38 mitogen-activated protein kinase (MAPK)-mediated myocardial tumor necrosis factor (TNF) production. METHODS: Langendorff perfused rat hearts (6/group) were subjected to oxidant stress (H2O2 infusion; 300 mmol/L x 80 minutes), with and without prior infusion of a specific P38 kinase MAPK inhibitor (P38i = 1 mmol/L/min x 5 minutes) or TNF neutralization (20 mg TNF binding protein (BP)/min x 80 minutes). Developed pressure (DP), coronary flow, and end-diastolic pressure were continuously recorded. Myocardial creatine kinase (CK) loss was measured in the coronary effluent, and tissue TNF was measured in myocardial homogenates. RESULTS: Eighty minutes of H2O2 infusion induced a 6.5-fold increase in myocardial TNF production, which was associated with a 70% decrease in DP and increase in CK loss. P38 MAPK inhibition or TNF-BP decreased myocardial TNF production, cardiomyocyte death, and myocardial dysfunction. CONCLUSIONS: These results demonstrate that H2O2 alone induces myocardial TNF production. P38 MPAK is an oxidant-sensitive enzyme that mediates oxidant-induced myocardial TNF production, cardiac dysfunction, and cardiomyocyte death.

The obligate role of protein kinase C in mediating clinically accessible cardiac preconditioning.

BACKGROUND: Cardiac preconditioning is an adaptation of cardiomyocytes that promotes tolerance to a subsequent ischemic insult. Adenosine receptor signaling is proposed as a mediator of preconditioning, but its mechanism of protection remains unknown. We hypothesized that protection against hypoxia-reoxygenation (H/R) injury could be conferred in a rat ventricle by adenosine-mediated protein kinase C (PKC) activation and that adenosine-mediated cardioprotection could be extended to human ventricular muscle. METHODS: Isolated rat and human ventricular muscle (VM) strips were subjected to 30 minutes of hypoxia and 60 minutes of reoxygenation (H/R control). The VM was pretreated with 125 mumol/L adenosine, an adenosine antagonist ((p-Sulfophenyl) theophylline [SPT] 50 mumol/L) and adenosine (adenosine + SPT), or with a PKC inhibitor (chelerythrine, 10 mumol/L) and adenosine (adenosine + chelerythrine) before H/R Developed force (DF) and tissue creatine kinase (CK) activity were assessed at end reoxygenation. Human trabeculae were obtained from diseased explanted hearts at cardiac transplantation and were also subjected to H/R injury. Human VM was pretreated with adenosine (125 mumol/L) before H/R injury. Results are expressed as mean +/- standard error of mean. RESULTS: In the rat, adenosine pretreatment conferred protection of DF against H/R injury (adenosine, 62% +/- 6%; H/R control, 27% +/- 2%, p < 0.05). Adenosine + SPT or adenosine + chelerythrine eliminated the functional recovery conferred by adenosine. This recovery of contractile function was associated with greater tissue CK activity (adenosine, 415 +/- 40 units/gm; H/R control, 78 +/- 13 units/gm, p < 0.05). The protective effects of adenosine against H/R were present in the human ventricle and with recovery of DF in adenosine (66% +/- 5%) and H/R control (24% +/- 4%), p < 0.05. CONCLUSIONS: Adenosine, a clinically accessible agonist, induces protection against H/R injury through a PKC-mediated mechanism in the rat ventricle. Further, the protection conferred by adenosine against H/R extends to the human ventricle.

Organ preconditioning.

The initial discovery of cardiac preconditioning has evolved into an exciting series of practical surgical applications. An enormous amount of evidence demonstrating both the safety and efficacy of ischemic preconditioning is available from animal studies. The challenging premise of intentionally subjecting patients and their organs to transient ischemia has acted as a formidable psychological and ethical impediment to the widespread clinical application of organ preconditioning. A more palatable alternative to ischemic preconditioning now involves approved medications designed to manipulate the cellular machinery mediating ischemic preconditioning. Pharmacologically induced preconditioning seems to confer equal organ protection. The relatively brief (but surgically relevant) window of protection provided by strategies such as ischemic preconditioning or adenosine agonists and potassium-adenosine triphosphate channel openers may, in the future, be extended. We have developed and reported the feasibility of liposomal delivery of heat shock protein to cardiac myocytes with subsequent protection against sepsis-induced dysfunction. Targeted strategies will ultimately broaden the therapeutic potential of organ preconditioning.

Neutrophils are required for endotoxin-induced myocardial cross-tolerance to ischemia-reperfusion injury.

BACKGROUND: Although polymorphonuclear neutrophilic leukocytes (PMNs) contribute to oxidative stress after endotoxemia, it is unknown whether preischemic PMN induction is required for endotoxin-mediated myocardial resistance to ischemia-reperfusion (I/R). OBJECTIVE: To determine whether neutrophils mediate endotoxin-induced myocardial cross-tolerance to I/R. DESIGN AND INTERVENTIONS: Rats received sublethal endotoxin (0.5 mg/kg intraperitoneally) with and without rabbit anti-rat PMN antibody (anti-PMN antibody, 0.15 mL intravenously, to achieve an absolute neutrophil count of < 200/microL) or antibody alone, 24 hours prior to global myocardial I/R (20-40 minutes, Langendorff mode). SETTING: The University of Colorado Surgical Research Laboratories, Denver. MAIN OUTCOME MEASURES: Myocardial developed pressure, coronary flow, end diastolic pressure, and time to ischemic contracture were recorded with a pressure amplifier-digitizer (MacLab, AD Instruments Inc, Milford, Mass). Myocyte damage was assessed by determining creatine kinase leakage in the coronary flow effluent by creatine kinase assay. RESULTS: Sublethal endotoxin induced cross-tolerance to I/R, as demonstrated by improved recovered developed pressure and coronary flow, and decreased time to ischemic contracture, end diastolic pressure, and creatine kinase leak (P < .05, analysis of variance and Bonferroni-Dunn). Anti-PMN antibody administered prior to sublethal endotoxin abolished these protective effects (P < .05). Polymorphonuclear neutrophil leukocyte depletion alone failed to abrogate the deleterious effects of I/R. CONCLUSIONS: (1) Sublethal endotoxin induces myocardial cross-tolerance to I/R; (2) PMN induction is required for endotoxin-mediated myocardial resistance to I/R; and (3) while myocardial I/R injury is equally severe after antibody-mediated PMN depletion, endotoxin-induced tolerance to I/R does not occur in the neutropenic host.

Potential gene therapy strategies in the treatment of cardiovascular disease.

Gene therapy is the introduction of new genetic material into somatic cells to synthesize missing or defective proteins. Efficient methods for the introduction of genetic material into cells are available, both in vitro and in vivo. These strategies involve chemical, physical, and viral-mediated mechanisms of gene transfer. Application of these gene transfer techniques has led to the development of potential gene-based treatment strategies that could combat vascular and myocardial disease. Gene therapy in the treatment of cardiovascular disease promises to alter atherosclerotic risk factors, prevent vascular thrombotic disease, retard progression of disease in the peripheral vasculature, provide drug delivery systems, and prevent myocardial infarction in patients with coronary artery disease. This exciting technology will eventually become the ultimate intervention in the treatment of cardiovascular disease.

Optimal myocardial preservation: cooling, cardioplegia, and conditioning.

Myocardial preservation techniques have evolved in conjunction with cardiac surgery and currently offer substantial protection against myocardial injury. We propose that cardiac preconditioning, a robust, endogenous mechanism of cardioprotection, is emerging as an important adjunct to current cardioplegic techniques. By reviewing the physiologic basis for current cardioplegic strategies, and understanding the cardioprotective benefits of preconditioning, we postulate that cardiac preconditioning may represent an important, clinically accessible component of myocardial protection.

Off-pump coronary artery bypass grafting decreases risk-adjusted mortality and morbidity.

BACKGROUND: The purpose of this study was to determine whether coronary artery bypass grafting without cardiopulmonary bypass (off-pump CABG) decreases risk-adjusted operative death and major complications after coronary artery bypass grafting in selected patients. METHODS: Using The Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database, procedural outcomes were compared for conventional and off-pump CABG procedures from January 1, 1998, through December 31, 1999. Mortality and major complications were examined, both as unadjusted rates and after adjusting for known base line patient risk factors. RESULTS: A total of 126 experienced centers performed 118,140 total CABG procedures. The number of off-pump CABG cases was 11,717 cases (9.9% of total cases). The use of an off-pump procedure was associated with a decrease in risk-adjusted operative mortality from 2.9% with conventional CABG to 2.3% in the off-pump group (p < 0.001). The use of an off-pump procedure decreased the risk-adjusted major complication rate from 14.15% with conventional CABG to 10.62% in the off-pump group (p < 0.0001). Patients receiving off-pump procedures were less likely to die (adjusted odds ratio 0.81, 95% CI 0.70 to 0.91) and less likely to have major complications (adjusted odds ratio 0.77, 95% CI 0.72 to 0.82). CONCLUSIONS: Off-pump CABG is associated with decreased mortality and morbidity after coronary artery bypass grafting. Off-pump CABG may prove superior to conventional CABG in appropriately selected patients.

Increased myocardial tumor necrosis factor-alpha in a crystalloid-perfused model of cardiac ischemia-reperfusion injury.

BACKGROUND: The heart is a tumor necrosis factor-alpha (TNF-alpha)-producing organ. Recent basic experimental and clinical evidence suggests that TNF-alpha is an important mediator of myocardial injury during acute myocardial infarction, chronic heart failure, cardiac allograft rejection, and cardiopulmonary bypass operations. Although it is known that the myocardium itself is capable of producing TNF-alpha in response to endotoxin, it is unknown whether there is an increase in myocardial tissue TNF-alpha levels after ischemia-reperfusion injury. We hypothesized that ischemia-reperfusion induces the production of TNF-alpha by the heart. METHODS: To avoid blood-borne TNF-alpha as a potentially confounding variable, we examined myocardial TNF-alpha production in a crystalloid-perfused model of cardiac ischemia-reperfusion injury. Isolated rat hearts were perfused with crystalloid solution and subjected to ischemia-reperfusion. Postischemic myocardial TNF-alpha was measured using an enzyme-linked immunosorbent assay and correlated with developed pressure, coronary flow, end-diastolic pressure, and creatine kinase loss (assay of activity in coronary effluent). RESULTS: Ischemia-reperfusion induced a marked increase in myocardial TNF-alpha that was associated with decreased myocardial contractility and coronary flow and with increased end-diastolic pressure and postischemic creatine kinase loss. CONCLUSIONS: The heart produces TNF-alpha in response to ischemia-reperfusion. Ischemia-induced TNF-alpha production may contribute to postischemic myocardial stunning, necrosis, or both. Strategies designed to limit ischemia-induced myocardial TNF-alpha production may have therapeutic utility in the settings of planned myocardial ischemic events.

Preconditioning and hypothermic cardioplegia protect human heart equally against ischemia.

BACKGROUND: The purpose of this study was to determine whether transient ischemic preconditioning protects human myocardium against normothermic ischemic injury. METHODS: Isolated human right atrial trabeculae were suspended in an organ bath with oxygenated Tyrode's solution at 37 degrees C and field stimulated at 1 Hz. Developed force was recorded. Trabeculae (Warm I/R) received normoxic perfusion before 45 minutes of normothermic simulated ischemia (hypoxic, substrate-free buffer with pacing at 3 Hz) and 120 minutes of reperfusion. Preconditioned trabeculae (Warm IPC) were subjected to 5 minutes of normothermic simulated ischemia and 10 minutes of perfusion before normothermic simulated ischemia-reperfusion injury. Trabeculae (Cold I/R) were subjected to hypothermic (4 degrees C) ischemia (hypoxic buffer) for 4 hours and 60 minutes of reperfusion (37 degrees C). Preconditioned trabeculae (Cold IPC) were pretreated with 5 minutes of normothermic simulated ischemia before hypothermic ischemia and 60 minutes of reperfusion. At the end of reperfusion, trabeculae were frozen at -70 degrees C and assayed for tissue creatine kinase activity. RESULTS: At the end of reperfusion, warm preconditioned trabeculae (Warm IPC) recovered 51% +/- 5% of baseline developed force, whereas warm I/R trabeculae recovered 24% +/- 3% (p < 0.05). Tissue creatine kinase levels reflecting preserved tissue viability were sustained in Warm IPC trabeculae (1,183 +/- 204 U/g), whereas nonpreconditioned control trabeculae (Warm I/R) exhibited lower levels of enzymatic activity (403 +/- 32 U/g) (p < 0.05). In contrast, Cold IPC trabeculae recovered 47% +/- 5% and Cold I/R, 56% +/- 8% of baseline developed force at the end of reperfusion (p > 0.05). CONCLUSIONS: We conclude that transient ischemic preconditioning protects human myocardium against normothermic ischemic injury.

Off-pump coronary artery bypass is associated with improved risk-adjusted outcomes.

BACKGROUND: The impact of off-pump median sternotomy coronary artery bypass grafting procedures on risk-adjusted mortality and morbidity was evaluated versus on-pump procedures. METHODS: Using the Department of Veterans Affairs Continuous Improvement in Cardiac Surgery Program records from October 1997 through March 1999, nine centers were designated as having experience (with at least 8% coronary artery bypass grafting procedures performed off-pump). Using all other 34 Veterans Affairs cardiac surgery programs, baseline logistic regression models were built to predict risk of 30-day operative mortality and morbidity. These models were then used to predict outcomes for patients at the nine study centers. A final model evaluated the impact of the off-pump approach within these nine centers adjusting for preoperative risk. RESULTS: Patients treated off-pump (n = 680) versus on-pump (n = 1,733) had lower complication rates (8.8% versus 14.0%) and lower mortality (2.7% versus 4.0%). Risk-adjusted morbidity and mortality were also improved for these patients (0.52 and 0.56 multivariable odds ratios for off-pump versus on-pump, respectively, p < 0.05). CONCLUSIONS: An off-pump approach for coronary artery bypass grafting procedures is associated with lower risk-adjusted morbidity and mortality.

Cardiac surgical implications of calcium dyshomeostasis in the heart.

The prevalence of coronary artery disease renders myocardial ischemia a leading cause of morbidity and mortality. Both cardiac bypass operations and cardiac transplantation cause myocardial ischemia and reperfusion injury. Intracellular calcium transport and regulation are of paramount importance in both normal and pathologic myocardial states. Calcium regulation is integral to nearly every myocyte function, from early development to senescence. Normal intracellular calcium-mediated excitation-contraction coupling and abnormal patterns of calcium regulation leading to systolic/diastolic dysfunction are now therapeutically accessible to the cardiac surgeon. Additionally, altered Ca2+ transport protein gene expression is a mechanism of myocardial dysfunction. Therapeutic strategies involve receptor-mediated transduction of signals to intracellular metabolic sites. Evidence implicates protein kinase C as well as a potential therapeutic role for Ca2+. The potential for pharmacologic access to this protective state has abundant clinical appeal. The protective state (cardiac "preconditioning") is transient but is amenable as therapy against operation-related ischemic events.

The role of intraaortic balloon counterpulsation in patients undergoing cardiac operations.

Intraaortic balloon counterpulsation (IABC) was used to assist 60 patients undergoing cardiac operations for reasons of acute left ventricular failure (18 patients) or electively for indications in high-risk coronary and valvular heart disease (42 patients). Nine of 18 patients achieved hemodynamic stability when treated for acute perioperative or postoperative cardiogenic shock. Four of these died from problems unassociated with postoperative left ventricular failure and 5 were long-term survivors, indicating a potential salvage of 50%. In 42 high-risk patients, IABC was used electively to control preinfarction angina before operation (21 patients) and prophylactically to prevent postoperative low-output failure in another 21 patients with severe coronary and valvular heart disease. Thirty-nine, or 93%, of these patients survived. There were no deaths in the preinfarction angina group, 1 death in the group with coronary disease and ejection fractions less than 30%, and 2 deaths in those with valvular heart disease and congestive failure. Seven patients developed thrombotic or ischemic complications, but no permanent damage resulted. IABC is an important form of assistance for any patient with preoperative, intraoperative, or postoperative left ventricular failure and adds safety and hemodynamic stability for the high-risk patient with preinfarction angina or poor ventricular function.