Does warm blood retrograde cardioplegia preserve right ventricular function?

BACKGROUND: Efficacy of warm blood retrograde cardioplegia in preserving right heart function remains controversial. The current study was conducted to gauge the preservation of right ventricular function after warm blood retrograde cardioplegia. METHODS: We studied 75 consecutive patients undergoing isolated heart valve procedures with warm blood retrograde cardioplegia as the exclusive mode of preservation. Right ventricular radionuclide ejection fraction and hemodynamic measurements using a pulmonary artery catheter were calculated before and within 3 days after operation. RESULTS: Postoperative radionuclide right ventricular ejection fraction was well preserved at 0.4686 +/- 0.0122 compared with 0.4327 +/- 0.0255 preoperatively (p = 0.7064). Right ventricular systolic work index improved from 5.82 +/- 0.52 to 8.97 +/- 0.60 g x m/m2 (p < 0.0001) and cardiac index increased from 2.40 +/- 0.09 to 2.92 +/- 0.11 L/m2 (p < 0.0001). When right ventricular systolic work index was correlated with preload, 30 patients moved up and down on the same ventricular function curve and 42 moved to a higher inotropic curve postoperatively. Only 3 patients demonstrated decreased inotropy. CONCLUSIONS: In the clinical setting warm blood retrograde cardioplegia used as the exclusive mode of myocardial preservation provides adequate protection of the right heart.

Does cardioplegia type affect outcome and survival in patients with advanced left ventricular dysfunction? Results from the CABG Patch Trial.

BACKGROUND: There is controversy regarding which cardioplegic solution, temperature, and route of administration provides superior protection. The CABG Patch Trial enrolled a high-risk group of coronary artery disease patients with an ejection fraction of <36%. Thus, they constitute an ideal group to benefit most from optimal cardioplegic protection. METHODS AND RESULTS: All patients randomized into the trial were compared with respect to the use of blood and crystalloid cardioplegia. In addition, a questionnaire was sent to surgeons requesting blood cardioplegic temperature and route. Patients receiving crystalloid cardioplegia versus those receiving blood cardioplegia were found to have significantly more operative deaths (2% versus 0.3%, P:=0.02), postoperative myocardial infarctions (10% versus 2%, P:<0.001), shock (13% versus 7%, P:=0. 013), and postoperative conduction defects (21.6% versus 12.4%, P:=0. 001). Despite this, early death (6% crystalloid versus 4% blood cardioplegia) and late death (24% crystalloid versus 21% blood cardioplegia) statistics were not significantly different. Patients receiving normothermic blood had less postoperative right ventricular dysfunction (10%) than did patients receiving cold blood (25%) or cold blood with warm reperfusion (30%) (P:=0.004). There was no significant difference in early or late death. Finally, patients who received combined antegrade and retrograde cardioplegia had significantly less inotrope use (71% versus 84%, P:=0.002), right ventricular dysfunction (23% versus 41%, P:=0.001), and postoperative balloon pump use (12% versus 19%, P:=0.02) than did those who received antegrade cardioplegia. There was no difference in survival. CONCLUSIONS: Blood cardioplegia and combined antegrade and retrograde cardioplegia are superior to crystalloid and antegrade cardioplegia alone for postoperative morbidity. Despite this, there is no significant difference in early or late survival.

Myocardial protection by preconditioning of heart with losartan, an angiotensin II type 1-receptor blocker: implication of bradykinin-dependent and bradykinin-independent mechanisms.

BACKGROUND: Ischemic preconditioning (PC) represents a state-of-the-art technique for myocardial preservation. Although certain intracellular mediators have been shown to play a role in PC, the exact nature of the trigger for PC is not known. Our previous study demonstrated that intracellular bradykinin released from the heart during ischemia/reperfusion plays a role in myocardial preservation. This study was undertaken to further examine the mechanism of bradykinin-mediated PC. METHODS AND RESULTS: Since the bradykinin B(2) receptor is likely to provide cardioprotection by blocking angiotensin II formation, we determined the effects of an angiotensin II type 1 (AT(1)) receptor blocker, losartan, and a bradykinin B(2) receptor blocker, HOE 140, on myocardial protection. Isolated rat hearts were perfused initially by the Langendorff mode with Krebs-Henseleit buffer (KHB) for 15 minutes in the absence (control) or presence of losartan (4.5 micromol/L) and/or HOE 140 (10 micromol/L). After conversion to the working mode for 10 minutes (baseline), randomly assigned control and experimental hearts were subjected to 30 minutes of normothermic global ischemia followed by 2 hours of reperfusion. Myocardial function, infarct size, cardiomyocyte apoptosis, and amount of bradykinin/angiotensin released from the hearts were measured at baseline and during reperfusion while in the working mode. Significant postischemic ventricular recovery was demonstrated by improved developed pressure and aortic flow and reduced myocardial infarct size and apoptotic cell death with losartan, whereas the reverse was true for HOE 140. The functional recovery and infarct size-lowering ability of losartan were partially blocked and the antiapoptotic function of losartan was completely blocked by HOE 140. CONCLUSIONS: The results document that losartan reduced whereas HOE 140 increased myocardial ischemia/reperfusion injury by blocking AT(1) and bradykinin B(2) receptors, respectively, suggesting a role of the bradykinin B(2) receptor in PC. Losartan provided cardioprotection through both bradykinin-dependent and bradykinin-independent mechanisms.

Risk of dysphagia after transesophageal echocardiography during cardiac operations.

BACKGROUND: Dysphagia can be a significant complication following cardiac operations. This study evaluates its incidence and relationship to intraoperative transesophageal echocardiography (TEE) for specific indications versus known factors such as stroke or prolonged intubation. METHODS: Records of 838 consecutive cardiac surgical patients were reviewed, and categorized into those who received TEE for specific indications versus those who did not (nonTEE). Dysphagia was recorded when symptoms were confirmed by barium cineradiography. Multiple logistic regression identified significant factors causing dysphagia. RESULTS: TEE was significantly related to the development of postoperative dysphagia by multiple logistic regression (p < 0.001). After controlling for other significant factors (stroke, left ventricular ejection fraction, intubation time, duration of operation), the odds of dysphagia for TEE patients was 7.8 times greater than for nonTEE patients. CONCLUSIONS: TEE may be an independent risk factor for dysphagia following cardiac operations.

Is there a relationship between systemic perfusion temperature during coronary artery bypass grafting and extent of intraoperative ischemic central nervous system injury?

OBJECTIVE: This study was designed to compare the volume of cerebral infarction in patients operated on under either hypothermic or tepid/normothermic perfusion for coronary revascularization. METHODS: A randomized trial with preoperative, postoperative, and late neurologic evaluation was conducted in patients undergoing coronary revascularization having either hypothermic or tepid/normothermic perfusion for coronary revascularization. The goal was to determine whether perfusion temperature correlated with neurologic dysfunction associated with coronary artery bypass. RESULTS: Twelve intraoperative ischemic strokes occurred during coronary revascularization in a series of 291 patients. Six of these were in the group receiving hypothermic perfusion and 6 in groups receiving the tepid/normothermic perfusion. Measuring the infarct volume documented that 3 of the strokes in each group resulted in minor or small infarcts and 3 in each group were significant, major strokes. The volume of infarction, whether including all 6 patients in each group or only those with major strokes, was no different between the hypothermic and the tepid/normothermic groups. CONCLUSIONS: In this series of 291 patients randomized to perfusion temperature, we observed no relationship between the size of a cerebral ischemic infarct and the perfusate temperature during coronary revascularization.

Molecular targets of gene therapy.

Ischemic reperfused heart represents a potential target for gene therapy because gene transfer can represent an alternate pharmacological approach to protect the heart from cellular injury. Gene therapy may be particularly useful to deal with previously unapproachable problems. For myocardial preservation, gene therapy could replace those pharmacological interventions when drugs are delivered locally by sustained release with the help of mechanical device, eg, implants. In this review, attempts are made to define the molecular targets for gene therapy primarily applicable to myocardial preservation associated with ischemia and reperfusion. It has been emphasized that for successful gene transfer, not only characterization of proper targets and elimination of undesirable side effects are necessary, but also the therapy must be proven superior compared to other pharmacological interventions including surgery.

Fenestrated felt facilitates anastomotic stability and safety in "off-pump" coronary bypass.

Metal stabilizing devices used in beating heart surgery, although largely effective, occasionally slip or cause lacerations of epicardial veins or myocardium, resulting in blood loss that requires time-consuming corrective maneuvers. The use of a fenestrated felt as a cushion in conjunction with the stabilizers eliminates slipping and/or trauma, thus facilitating coronary anastomoses on the beating heart.

Influence of cardiopulmonary bypass perfusion temperature on neurologic and hematologic function after coronary artery bypass grafting.

BACKGROUND AND METHODS: A National Institutes of Health-sponsored trial (1994 to 1998) randomized patients undergoing coronary artery bypass grafting that required three or more grafts to receive perfusion at either cold (20 degrees C), tepid (32 degrees C), or warm (37 degrees C) temperature. The goal of the study was to evaluate morbidity, primarily neurologic dysfunction and secondarily hematologic factors. One thousand seven hundred seventy-seven patients were screened and 291 enrolled. Neurologic function was studied by a dedicated pool of blinded neurologists. A standard test battery termed the Mathew Scale using three subscales--cognitive function, elemental skills, and disability--was used to study central nervous system function. Hematologic function was assessed in 53 of the 291 patients with measurements of postoperative fibrinolytic potential. RESULTS: All preoperative and operative data were comparable between groups. A decrease in Mathew Scale was seen in 69% of patient from before operation to immediately after operation. However, between the early postoperative study and the 1-month follow-up, 48% of patients had returned to baseline. There was no difference noted across temperature groups in any neurologic parameter of function. In all, 55% of the group were at or above their preoperative level at 1 month. Forty-nine patients suspect for cerebrovascular accident had a computed tomographic scan, but only 13 (4.5%) had a documented cerebrovascular accident (4 patients in the warm, 3 in the tepid, and 6 patients in the cold group). Fibrinolytic changes correlated with perfusion temperature documented that fibrinolysis was most active at 37 degrees C. Thus, increasing perfusate temperature increases fibrinolysis, which was associated with reoperation for bleeding in 4% warm group patients, 1% tepid, and 0% cold group patients (0.1 > p > 0.05). No other perioperative complications were temperature related. There were 4 deaths (1.4%) (1 in the warm group, 2 in the tepid group, and 1 in the cold group). CONCLUSIONS: (1) Persistent postoperative neurologic dysfunction at 1 month occurs in 36% of patients undergoing coronary artery bypass grafting and is not related to a cerebrovascular accident; 2) perfusion temperature has no relationship to neurologic function after bypass; and 3) fibrinolytic activity is greatest at warm temperatures.

The 'primeless pump': a novel technique for intraoperative blood conservation.

PURPOSE: Hemodilution during cardiopulmonary bypass may lead to anemia requiring intraoperative transfusions. Prime removal from the cardiopulmonary bypass circuit was used to limit dilution and intraoperative transfusions. METHODS: The technique of prime removal consists of arterial and then venous side evacuation of crystalloid prior to cardiopulmonary bypass. The effectiveness of this technique, to maintain a higher hematocrit and reduce intraoperative transfusions, was studied prospectively in two consecutive groups of patients undergoing coronary revascularization (controls versus primeless). RESULTS: Intraoperative hematocrits were significantly higher (P < 0.0001) and transfusions lower (4%) in the primeless versus the control group (19%) (P = 0.003). Prime removal is of particular benefit in anemic (hematocrit < or = 35%) and/or small patients (body surface area < or = 2 m2). CONCLUSION: The technique of prime removal is simple, safe and cost-effective, reducing intraoperative transfusions, especially in small and/or anemic patients. It could be part of blood conservation strategies in most adult cardiac operations.

Influence of the preoperative signal-averaged electrocardiogram on left ventricular function after coronary artery bypass graft surgery in patients with left ventricular dysfunction. The CABG Patch Trial.

Patients with ischemic left ventricular (LV) dysfunction often have an improved survival and life quality after coronary artery bypass grafting (CABG), in part due to an improvement in LV function. A lack of LV ejection fraction (EF) improvement postoperatively portends a worse prognosis. Recently, an abnormal preoperative signal-averaged electrocardiogram (SAECG) in patients with a severely depressed LV ejection fraction undergoing elective CABG was shown to be associated with a higher early and late postoperative mortality. The present study evaluated patients with severe LV dysfunction to identify any relation between an abnormal preoperative SAECG and postoperative changes in LV function after successful CABG. Forty-five patients with LV dysfunction (LVEF <0.36) scheduled for elective CABG underwent preoperative SAECG and both pre- and postoperative LVEF determinations using radionuclide scans. Thirty-one patients in the group had an abnormal preoperative SAECG and 14 patients had a normal preoperative SAECG. Baseline patient characteristics were similar in both groups and the mean preoperative LVEF was 0.26. Overall, LVEF improved 31% postoperatively with a significantly greater benefit noted in the group with a normal baseline SAECG (14.9+/-5.7-point vs 4.8+/-8.5-point increase, p <0.001). All patients whose LVEF did not improve or worsened postoperatively had an abnormal preoperative SAECG. No SAECG measure was altered significantly by the operation. A preoperative SAECG provides information on the postoperative functional recovery of ischemic myocardium.

A cost-effective retractor and heart stabilizer for minimal-access coronary bypass.

Exposure for internal mammary artery harvesting and immobilization of the coronary artery during the performance of minimally invasive direct coronary artery bypass grafting requires the use of appropriate retractors and instruments. We have successfully used existing retractors and instruments, modified for such use, which are reusable and cost effective. The use of such a retractor and cardiac stabilizer is described.

Echocardiography allows safer venous cannulation during excision of large right atrial masses.

BACKGROUND: Excision of large right atrial masses requires bicaval cannulation and cardiopulmonary bypass. Safe venous cannulation can be accomplished only by knowing the exact intracavitary location and extension of the mass to avoid fragmentation. Transthoracic echocardiography and intraoperative transesophageal echocardiography, although helpful, cannot always define the exact intracavitary relationships of the tumor. METHODS: We have used both intraoperative transesophageal and epicardial echocardiography to guide venous cannulation in 4 patients with large right atrial masses. Both echo images are used by the surgeon to select the exact site and method of cannulation to avoid fragmentation of the mass. Epicardial echocardiography complemented the images obtained by transesophageal echocardiography. RESULTS: The technique of combined transesophageal and epicardial echocardiography allowed safe venous cannulation in all 4 patients. Each of the right atrial masses was safely excised using case-specific cannulation techniques guided by the echocardiographic images. CONCLUSIONS: We propose the routine use of both intraoperative transesophageal and epicardial echocardiography in guiding venous cannulation for safe excision of large right atrial masses.

What is the best perfusion temperature for coronary revascularization?

BACKGROUND: [corrected] A National Institutes of Health-funded clinical trial of patients undergoing coronary artery bypass randomized perfusate and myocardial preservation to cold, tepid, or warm temperatures. The goal of the trial was to evaluate neurologic function before and after operation (4 days and 1 month after operation) and to measure hematologic data for fibrinolytic potential. METHODS: The three groups comprised 116 patients who completed neurologic evaluation by means of the Mathew scale out of 130 entered into the trial (37 cold group, 50 tepid, and 43 warm). Twenty-five patients had complete hematologic studies done. All three groups were comparable before operation. The myocardial preservation protocol used blood cardioplegic solution at cold (8 degrees to 10 degrees C), tepid (32 degrees C), or warm (37 degrees C) temperature and the systemic perfusate temperature during cardiopulmonary bypass was 20 degrees (cold), 32 degrees C (tepid), or 37 degrees (warm). RESULTS: Patients in the cold group had a longer duration of intubation and postoperative hospitalization and a slightly but significantly higher peak postoperative creatine kinase MB level than patients in the warm group. There were no deaths. There was deterioration in Mathew scale findings in all three groups, and no distinction could be made between groups. However, a significantly higher number in the cold group had an abnormal postoperative neurologic examination result that prompted computed tomographic scanning (18.9% cold, 2% tepid, 9.3% warm). A cerebrovascular accident was documented by computed tomographic scanning in 8.1%, 0%, and 4.7% of patients in the cold, tepid, and warm groups, respectively (not significant). Hematologic data documented significantly increased fibrinolytic potential in the warm group. CONCLUSIONS: Perfusion temperature is a factor in recovery from cardiopulmonary bypass. Cold has more adverse neurologic sequelae that prompt computed tomographic scanning whereas warm has more activation of fibrinolytic potential. Tepid is the best temperature for optimizing recovery from cardiopulmonary bypass.

Nitric oxide/carbon monoxide. A molecular switch for myocardial preservation during ischemia.

BACKGROUND: In heart, NO is produced from L-arginine catalyzed by NO synthase, and CO is formed during the conversion of bilirubin from heme by the action of heme oxygenase. NO, which exerts its biological actions through cGMP and heme, has recently been implicated in myocardial protection during ischemia and reperfusion. We hypothesized that the intracellular signaling by NO may be modulated by heme oxygenase. METHODS AND RESULTS: To test this hypothesis, isolated rat hearts were perfused for 10 minutes with one of the following: (1) buffer alone; (2) 3 mmol/L L-arginine, a precursor for NO; (3) 650 mumol/L zinc protoporphyrin, a heme oxygenase inhibitor; (4) 3 mmol/L L-arginine plus 650 mumol/L zinc protoporphyrin; (5) 15 mumol/L methylene blue, a cGMP inhibitor; or (6) 3 mmol/L L-arginine plus 15 mumol/L methylene blue. Hearts were then made ischemic for 30 minutes, followed by 30 minutes of reperfusion. L-Arginine afforded significant myocardial protection, as evidenced by increased developed pressure (DP) (53.3 +/- 4.3 versus 35.4 +/- 1.8 for control), dP/dtmax (2405 +/- 125 versus 1758 +/- 117 for control), aortic flow (23 +/- 1.5 versus 9.4 +/- 1.6 for control), and coronary flow (CF) (23.0 +/- 0.8 versus 19.0 +/- 1.6 for control) at the end of reperfusion. Protoporphyrin tended to reduce these values compared with L-arginine alone (DP, 27.5 +/- 1.4; dP/dtmax, 1400 +/- 78; CF, 17 +/- 0.5), suggesting a contribution of heme oxygenase in addition to NO for myocardial preservation. Increased mRNAs for the heme oxygenase were noticed in the ischemic reperfused myocardium. Contents of cGMP, the second messenger for NO signaling, increased in the L-arginine group (1.6 +/- 0.1 versus 1.1 +/- 0.1 for control) and were reduced by protoporphyrin. cGMP was completely inhibited by methylene blue, which also retarded postischemic myocardial functional recovery. Malonaldehyde formation, a presumptive marker for free radical generation, was decreased in the L-arginine group (0.053 +/- 0.003) compared with control (0.089 +/- 0.005) but was increased in the protoporphyrin group (0.09 +/- 0.003) compared with the L-arginine group. In vitro studies demonstrated that NO was able to reduce the reactive oxygen species produced by myoglobin, especially oxoferrylmyoglobin, which either are present in heart or are formed in high concentrations during the reperfusion of ischemic myocardium. CONCLUSIONS: The results suggest that NO contributes to myocardial preservation by both cGMP-dependent and cGMP-independent mechanisms, the former being modulated by CO signaling and the latter by virtue of its antioxidant action.

Critical timing of nitric oxide supplementation in cardioplegic arrest and reperfusion.

BACKGROUND: It has been shown that increased nitric oxide (NO) generation is associated with improved myocardial preservation during ischemia/reperfusion. This study sought to determine the optimal timing for NO supplementation in the setting of cardioplegic arrest, regional ischemia, and reperfusion. METHODS AND RESULTS: Isolated working rat hearts were arrested with normothermic oxygenated potassium cardioplegia for 5 minutes, followed by 60 minutes of normothermic continuous cardioplegic administration with left anterior descending coronary artery (LAD) occlusion. The hearts were divided into four groups. Hearts in group 1 were ischemic/reperfused controls without L-arginine treatment. Hearts in group 2 were perfused with 3 mmol/L L-arginine for 5 minutes before cardioplegic arrest. Hearts in group 3 were perfused with 3 mmol/L L-arginine in the cardioplegia solution. Hearts in group 4 were perfused with 3 mmol/L L-arginine for 5 minutes only during initial reperfusion. Myocardial contractile function after 30 minutes of reperfusion was significantly better in group 2 compared with the other groups and was significantly lower in group 4 than group 1. Coronary flow, although decreased from base line in all groups at 30 minutes of reperfusion, was highest in group 2. The tissue accumulation of cGMP in groups 2 and 3 increased significantly after L-arginine infusion compared with the control group (group 1). In contrast, the LAD regional cGMP after reperfusion in group 4 was comparable to group 1 and significantly lower than groups 2 and 3, whereas the circumflex region cGMP in group 4 was significantly increased over group 1, comparable to groups 2 and 3. LDH release in groups 2 and 3 was significantly lower compared with groups 1 and 4. CONCLUSIONS: As assessed by myocardial function and LDH release, L-arginine is most beneficial when given before cardioplegic arrest, effective during cardioplegic arrest, and detrimental during reperfusion. This suggests that L-arginine given during reperfusion is deleterious to optimal recovery of myocardial function in this ischemic model and that the effect of NO generation in the ischemic/reperfused myocardium may be dependent on the condition of the endothelium.

Does interruption of normothermic cardioplegia have adverse effects on myocardium? A retrospective and prospective clinical evaluation.

A total of 154 patients who underwent isolated coronary revascularization (coronary artery bypass grafting) using retrograde, near-continuous, warm cardioplegia for myocardial protection, were arbitrarily divided into three groups according to the cumulative cardioplegic interruption (i.e. the sum total of all the short cardioplegic interruption periods, expressed as a percentage of the cardiac arrest period). Group 1 (39 patients) had < 20% interruption (mean(s.e.m.) 12.5(0.01)%), group 2 (82 patients) had 20-39% interruption (mean(s.e.m.) 30.1(0.01)%) and group 3 (33 patients) had > 40% interruption (mean(s.e.m.) 45.4(0.01%). The three groups were comparable except for longer clamp time in group 3 and a lower cardiac index in group 1. The mean number and duration of cardioplegic interruptions and reperfusions and multiple clinical outcomes were recorded. Clinical outcomes (Q) wave perioperative infraction, use of an intra-aortic balloon pump, mortality, and length of stay in the intensive care unit and hospital) were the same in all groups despite significant differences in percent, number and duration of interruption and reperfusion as well as cardiac arrest. The only significant differences found were in the level of creatine kinase-MB (CK-MB) and use of inotropes after surgery, both being higher in group 1 than in groups 2 and 3 (which is the opposite of what would be expected). Intraoperative hemodynamic (cardiac index and left ventricular ejection fraction) and metabolic evaluations (CK-MB, lactate production and oxygen extraction) in 22 additional patients who underwent coronary artery bypass grafting showed no significant differences between two groups having < 30% versus > 30% cumulative cardioplegic interruption. It is concluded that warm cardioplegic interruption as used clinically has no adverse effects on the myocardium in patients undergoing coronary revascularization. Warm retrograde near-continuous blood cardioplegia is an effective method of myocardial protection.

L-arginine reduces endothelial inflammation and myocardial stunning during ischemia/reperfusion.

BACKGROUND: This study evaluated whether the nitric oxide precursor L-arginine could reduce ischemia/reperfusion injury by preventing leukocyte-endothelial interactions. METHODS: Normothermic regional ischemia was induced in the open-chest working pig heart for 30 minutes followed by 90 minutes of reperfusion. A preischemic 10-minute intravenous infusion of 4 mg.kg-1.min-1 of L-arginine (n = 12) was compared with 12 control pigs. Nitric oxide release was measured from the coronary sinus using an amperometric probe. Left ventricular function, malonaldehyde, creatine kinase, myocardial oxygen extraction, and the soluble adhesion molecules (intracellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1) were measured. RESULTS: Nitric oxide release was significantly reduced from baseline throughout ischemia/reperfusion only in the control group. Systolic and diastolic function, and myocardial oxygen extraction were also significantly decreased during early reperfusion in the control compared with the L-arginine group. Peak creatine kinase release was not significantly different between groups. The incidence of ventricular fibrillation, malonaldehyde release, and soluble intracellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1 were each significantly decreased during reperfusion in the L-arginine group. CONCLUSIONS: L-Arginine reduced lipid peroxidation, plasma levels of soluble adhesion molecules, myocardial stunning, and arrhythmias. These results support an excessive endothelial injury/inflammatory response after regional ischemia/reperfusion that can be ameliorated through augmented nitric oxide.

Drug-induced heat-shock preconditioning improves postischemic ventricular recovery after cardiopulmonary bypass.

BACKGROUND: Heat-stress preconditioning of mammalian heart has been found to confer protection against ischemic reperfusion injury. Heat shock is generally provided by warming the animal by mechanical means, which is often impractical in a clinical setting. Amphetamine, a sympathomimetic drug, can elevate the body temperature as a result of enhanced endogenous lipolysis. In this study, we examined the effects of heat shock induced by amphetamine on postischemic myocardial recovery in a setting of coronary revascularization for acute myocardial infarction. METHODS AND RESULTS: Adult Yorkshire swine were injected with amphetamine (3 mg/kg IM) (n = 12), and body temperature was continuously monitored. For control studies, the pigs were injected with saline (n = 12). Five swine in each group were killed after 3 hours to obtain biopsies of vital organs to measure heat-shock protein (HSP) mRNAs. After 40 hours, the remaining 7 pigs in each group were placed on cardiopulmonary bypass, and the isolated, in situ heart preparations were subjected to 1 hour of occlusion of the left anterior descending coronary artery followed by 1 hour of global hypothermic cardioplegic arrest and 1 hour of reperfusion. Postischemic myocardial performance was monitored by measuring left ventricular (LV) pressure, its dP/dt, myocardial segment shortening, and coronary blood flow. Cellular injury was examined by measurement of creatine kinase release. The antioxidant enzymes superoxide dismutase and catalase were also assayed. Amphetamine treatment was associated with the induction of mRNAs for HSP 27, HSP 70, and HSP 89 in all the vital organs, including heart, lung, liver, kidney, and brain. Amphetamine also enhanced superoxide dismutase and catalase activities in the heart. Significantly greater recovery of LV contractile functions was noticed, as demonstrated by improved recovery of LV developed pressure (61% versus 52%), LV dP/dtmax (52% versus 44%), and segment shortening (46.2% versus 10%) and reduced creatine kinase release in the amphetamine group. CONCLUSIONS: The results demonstrate that amphetamine can induce whole-body heat shock that can precondition the heart, enhancing cellular tolerance to ischemia-reperfusion injury. Amphetamine is a sympathomimetic drug that may be used for preconditioning.