Predicting the survival of experimental ischaemic small bowel using intraoperative near-infrared fluorescence angiography.

BACKGROUND: Predicting the long-term viability of ischaemic bowel during surgery is challenging. The aim was to determine whether intraoperative near-infrared angiography (NIR-AG) of ischaemic bowel might provide metrics that were predictive of long-term outcome. METHODS: NIR-AG using indocyanine green was performed on 24 pigs before, and after inducing bowel ischaemia to determine the feasibility of NIR-AG for detecting compromised perfusion. Contrast-to-background ratio (CBR) over time was measured in regions of interest throughout the bowel, and various metrics of the CBR-time curve were developed. Sixty rat small bowels, with or without strangulation, were imaged during surgery and on day 3 after operation. CBR metrics and clinical findings were assessed quantitatively for their ability to predict animal survival, histological grade of ischaemic injury and visible necrosis on day 3. RESULTS: In ischaemic pig small bowel, various qualitative and quantitative CBR metrics appeared to correlate with bowel injury as a function of distance from normal bowel. In rats, intraoperative clinical assessment showed high specificity but low sensitivity for predicting outcome on day 3 after operation. Qualitative patterns of the CBR-time curve, such as absence of an arterial inflow peak and presence of a NIR filling defect, resulted in better prediction of survival (90 per cent), histological grade (85 per cent) and visible necrosis on day 3 (92 per cent). CONCLUSION: Survival of ischaemic bowel was predicted by intraoperative NIR-AG with greater accuracy than clinical evaluation alone.

Intraoperative detection of cell injury and cell death with an 800 nm near-infrared fluorescent annexin V derivative.

The intraoperative detection of cell injury and cell death is fundamental to human surgeries such as organ transplantation and resection. Because of low autofluorescence background and relatively high tissue penetration, invisible light in the 800 nm region provides sensitive detection of disease pathology without changing the appearance of the surgical field. In order to provide surgeons with real-time intraoperative detection of cell injury and death after ischemia/reperfusion (I/R), we have developed a bioactive derivative of human annexin V (annexin800), which fluoresces at 800 nm. Total fluorescence yield, as a function of bioactivity, was optimized in vitro, and final performance was assessed in vivo. In liver, intestine and heart animal models of I/R, an optimal signal to background ratio was obtained 30 min after intravenous injection of annexin800, and histology confirmed concordance between planar reflectance images and actual deep tissue injury. In summary, annexin800 permits sensitive, real-time detection of cell injury and cell death after I/R in the intraoperative setting, and can be used during a variety of surgeries for rapid assessment of tissue and organ status.

Modified Glenn connection for acutely ischemic right ventricular failure reverses secondary left ventricular dysfunction.

BACKGROUND: Right heart failure after cardiopulmonary bypass can result in severe hemodynamic compromise with high mortality, but the underlying mechanisms remain poorly understood. After ischemia-induced right ventricular failure, alterations in the interventricular septal position decrease left ventricular compliance and limit filling but may also distort left ventricular geometry and compromise contractility and relaxation. This study investigated the effect of acute isolated right ventricular ischemia on biventricular performance and interaction and the response of subsequent right ventricular unloading by use of a modified Glenn shunt. METHODS: In 8 pigs isolated right ventricular ischemic failure was induced by means of selective coronary ligation. A modified Glenn circuit was then established by a superior vena cava-pulmonary artery connection. Ventricular performance was determined by conductance catheter-derived right ventricular pressure-volume loops and left ventricular pressure-segment length loops. Hemodynamic data at baseline, after right ventricular ischemia, and after institution of the Glenn circuit were obtained during inflow occlusion, and the load-independent contractile indices were derived. RESULTS: Right ventricular free-wall ischemia resulted in acute right ventricular dilation (118 +/- 81 mL vs 169 +/- 70 mL, P =.0008) and impairment of left ventricular contractility indicated by the reduced end-systolic pressure-volume relation slope (50.0 +/- 19 mm Hg/mm vs 18.9 +/- 8 mm Hg/mm, P =.002) and preload recruitable stroke work index slope (69.6 +/- 26 erg x cm(-3) x 10(3) vs 39.7 +/- 13 erg x cm(-3) x 10(3), P =.003). In addition, left ventricular relaxation (tau) was significantly prolonged (33.3 +/- 10 ms vs 53.0 +/- 16 ms, P =.012). Right ventricular unloading with the Glenn shunt reduced right ventricular dilation and significantly improved left ventricular contraction, end-systolic pressure-volume relation slope (18.9 +/- 8 mm Hg/mm vs 35.8 +/- 18 mm Hg/mm, P =.002), preload recruitable stroke work index slope (39.7 +/- 26 erg x cm(-3) x 10(3) vs 63.0 +/- 22 erg x cm(-3) x 10(3), P =.003), and diastolic performance (tau 53.0 +/- 16 ms vs 43.5 +/- 13 ms, P =.001). CONCLUSIONS: Right ventricular ischemia-induced dilation resulted in acute impairment of left ventricular contractility and relaxation. A modified Glenn shunt attenuated the left ventricular dysfunction by limiting right ventricular dilation and restoring left ventricular cavity geometry.

Excimer versus carbon dioxide transmyocardial laser revascularization: effects on regional left ventricular function and perfusion.

BACKGROUND: Transmyocardial laser revascularization (TMR) has been established with the carbon dioxide (CO2) laser. The largely unstudied excimer laser creates channels through chemical bond dissociation instead of thermal ablation, thereby avoiding thermal injury. We sought to compare the effects of CO2 and excimer TMR in a porcine model of chronic ischemia. METHODS: Pigs underwent ameroid constrictor placement on the circumflex artery to create chronic ischemia. TMR was performed with CO2 (n = 8) or excimer (n = 8) laser 6 weeks later; controls (n = 7) had ameroid placement only. Regional myocardial blood flow (RMBF), determined by radioactive microspheres, and regional myocardial function, determined by percent segmental shortening (%SS), were assessed 18 weeks after ameroid placement. RESULTS: Values are mean +/- SD. In the ischemic zone, RMBF (mL/min/g) was improved in the CO2 (0.73 +/- 0.19) and excimer (0.78 +/- 0.22) groups when compared with controls (0.55% +/- 0.12%, p < 0.05). %SS was also improved in the CO2 (15.2% +/- 5.5%) and excimer (15.3% +/- 5.1%) groups when compared with controls (8.0% +/- 4.2%, p < 0.05). CONCLUSIONS: Excimer and CO2 TMR significantly improve RMBF and regional function in this porcine model of chronic myocardial ischemia despite fundamentally different tissue interactions.

LV-powered coronary sinus retroperfusion reduces infarct size in acutely ischemic pigs.

BACKGROUND: We developed a prosthetic left ventricle (LV) to coronary sinus (CS) shunt (LVCSS) that is autoregulating and provides LV-powered retrograde perfusion of the coronary sinus. METHODS: Each of 20 Yorkshire pigs underwent 1 hour of left anterior descending diagonal artery occlusion followed by 3 hours of reperfusion. The controls (n = 5) did not have shunt treatment. The LVCSS group (n = 9) underwent shunt treatment during the ischemic period. The LVCSS with partial coronary sinus occlusion (PCSO) group (LVCSS+PCSO, n = 6) underwent shunt treatment and PCSO during the ischemic period. Vital staining and planimetry techniques were used to determine the area at risk for infarction and the area of necrosis. RESULTS: The area at risk was not significantly different among groups. The area of necrosis was decreased by 53% in the LVCSS group and by 73% in the LVCSS+PCSO group when compared to controls (p<0.01 among all groups). CONCLUSIONS: The LVCSS reduces infarct size in pigs after acute coronary artery occlusion. The addition of PCSO to LVCSS further improves myocardial salvage.

An engineering model of dynamic cardiomyoplasty. I.

Dynamic cardiomyoplasty (DCM) is an emerging surgical procedure for heart failure in which the patient's latissimus dorsi (LD) muscle is wrapped around the heart and stimulated to contract in synchrony with the heartbeat as a cardiac assist measure. A 6 week training protocol of progressive electrical stimulation renders the normally fatigueable skeletal muscle fatigue-resistant and suitable for chronic stimulation. To date, over 500 procedures have been performed in worldwide clinical trials. Investigators typically report symptomatic improvement and modest hemodynamic improvement in patients. Controversy exists regarding the exact mechanism of DCM. To test the hypothesis that DCM augments cardiac stroke volume through improvement in systolic function, we formulated an engineering model of dynamic cardiomyoplasty to predict stroke volume. The heart and the LD were modeled as nested (series) elastance chambers, and the vasculature was represented by a two-element Windkessel model. Using five healthy goats, we verified model predictions of stroke volume for both stimulator ON beats (y = 1.00x-0.08, r = 0.87, p < 0.0001) and OFF beats (y = 1.01x+1.06, r = 0.91, p < 0.0001), where x and y are the measured and predicted stroke volumes, respectively. The model confirms that using untrained latissimus dorsi applied to the normal myocardium produces only moderate increases in stroke volume and suggests that future research should focus on increasing LD strength after training.

An engineering model of dynamic cardiomyoplasty. II. Clinical applications.

Previously, a modification to the Sunagawa engineering model for the isolated left ventricle and arterial system was proposed and validated for dynamic cardiomyoplasty in an acute goat preparation. To test the hypothesis that this model may be applied to the clinical scenario in cardiomyoplasty patients, we predicted human stroke volume using the model with human clinical data from the literature. Predicted stroke volume correlated well with published stroke volume in patients who have had the dynamic cardiomyoplasty procedure. These results suggest that the modest hemodynamic improvement commonly reported after the procedure is performed may be due to diminished latissimus dorsi strength after transformation. The validity of both the original Sunagawa model and the previously proposed modification for dynamic cardiomyoplasty is further supported with these results. A nomogram methodology for predicting stroke volume after dynamic cardiomyoplasty for any particular patient is presented.

Innovative techniques in skeletal muscle cardiac assistance: first experimental study on minimally invasive aortomyoplasty and cardiomyoplasty.

Skeletal muscle cardiac assistance as a treatment modality for heart failure is considered a high-risk procedure subject to strict patient selection. The aim here is to develop minimally invasive techniques to improve surgical outcomes and increase clinical indications. Ten goats (45-55 kg) were studied. In six, the latissimus dorsi muscle (LDM) was harvested via an open technique on one side vs a minimally invasive technique on the other using video assistance through two 3 cm incisions. Surgical maneuvers and length of procedures were noted. Animals were recovered, observed daily for local complications, and killed after 1 week for comparative anatomic and histopathologic studies. In four other goats, minimally invasive aortomyoplasty or cardiomyoplasty was performed using video assistance (2 aortomyoplasty, 2 cardiomyoplasty). In this experimental series, there were no surgical complications. The minimally invasive LDM harvest required a mean of 81 min (range 55-116 mn) with no gross evidence of muscle damage. The technique of LDM harvesting was standardized and is reproducible. Aortic and cardiac wraping were also achieved through three ports and a left minithoracotomy of 4 cm, using the right or left LDM. A scarf technique for the descending aortomyoplasty using the left LDM, and an anterior wrapping for cardiomyoplasty using the left or right LDM was technically feasible with video assistance. This study suggests future clinical applicability.

Right latissimus dorsi cardiomyoplasty improves left ventricular energetics.

BACKGROUND: The mechanism by which cardiomyoplasty appears to enhance left ventricular (LV) function is not well understood. We applied the time-varying elastance model to study the effect of cardiomyoplasty on LV function, ventriculovascular coupling, and LV energetics in an acute canine model. METHODS: Right latissimus dorsi cardiomyoplasty was performed in 5 dogs. The end-systolic pressure-volume relation was generated by using brief caval occlusions. End-systolic elastance, effective arterial elastance, stroke work, internal work, total mechanical work, and stroke work efficiency (stroke work/total mechanical work) were calculated from these pressure-volume data. Myocardial oxygen consumption and overall mechanical efficiency (stroke work/myocardial oxygen consumption) were predicted using the myocardial oxygen consumption-total mechanical work relation. RESULTS: Skeletal muscle contraction significantly increased end-systolic elastance, an index of contractility. Although stroke work did not change significantly, the increase in end-systolic elastance led to a 29% decrease in total mechanical work, a 50% decrease in internal work, and an increase in stroke work efficiency from 53% to 66%. This was consistent with the observed 29% decrease in effective arterial elastance/end-systolic elastance, an indicator of ventriculovascular coupling that is related inversely to stroke work efficiency. Predicted myocardial oxygen consumption decreased by at least 22%, and predicted overall mechanical efficiency increased at a minimum from 16.1% to 18.4%. CONCLUSIONS: These results support the theory that cardiomyoplasty unloads the LV by decreasing LV volumes and increasing contractility. These effects appear to improve LV energetics by decreasing total mechanical work without significantly affecting stroke work, resulting in improved stroke work efficiency. The decrease in total mechanical work strongly suggests a decrease in myocardial oxygen consumption and an increase in overall mechanical efficiency.

Thoracoscopic transmyocardial laser revascularization.

BACKGROUND: Transmyocardial laser revascularization is a promising surgical technique used to treat nonreconstructable ischemic heart disease. Recent clinical data show that this technique improves the regional perfusion of ischemic myocardium and reduces angina. Presently, transmyocardial laser revascularization requires an open, lateral thoracotomy. We report here the use of thoracoscopic techniques to perform transmyocardial laser revascularization in a closed chest fashion. METHODS: Five Yorkshire farm pigs underwent left chest thoracoscopic exploration and pericardiotomy. A specialized laser handpiece then was introduced into the chest and thoracoscopic transmyocardial laser revascularization was performed (one channel per square centimeter) using an 800-W CO2 laser. RESULTS: Video analysis and gross pathology revealed that the anatomic area accessible to thoracoscopic transmyocardial laser revascularization included the entire left ventricular free wall distributions of the left anterior descending, left circumflex, and posterior descending arteries, from base to apex. Standard hematoxylin and eosin staining confirmed the creation of complete and patent 1-mm-diameter transmural channels throughout these distributions. CONCLUSION: We have shown that transmyocardial laser revascularization can be performed effectively and safely by thoracoscopy, and that this less invasive technique may reduce morbidity and provide a more cost-effective alternative therapy for nonreconstructable ischemic heart disease.

Decreased myocardial oxygen consumption indices in dynamic cardiomyoplasty.

BACKGROUND: To investigate the theory of decreased myocardial oxygen consumption (MVo2) in dynamic cardiomyoplasty (DCM), previous studies have calculated indices of MVo2 in DCM. These previous studies, however, used left ventricular pressure in formulas that assumed the assumed the heart to be in its native state, with the reference pressure at the epicardium assumed to be atmospheric. In DCM, however, the reference pressure at the epicardium is no longer atmospheric but rather is the compressive pressure generated by the latissimus dorsi (LD). We therefore used the transmural myocardial pressure, Pt, to calculate indices of MVo2 in DCM. METHODS AND RESULTS: A half-ellipsoidal, fluid-filled balloon was interposed between the LD and myocardium in a balloon-mediated cardiomyoplasty procedure in five goats. With commonly used LD stimulation parameters, Pt was calculated as left ventricular pressure minus balloon luminal pressure. Using Pt, the transmural tension time index (TtTI) and transmural pressure volume area (PtVA) were calculated. In another series of four goats, LD stimulation parameters were optimized and the TtTI and PtVA recalculated. With standard LD stimulation parameters, the TtTI decreased by 48%, from 15.8 to 8.2 mm Hg.s, and the PtVA by 21%, from 775 to 612 mm Hg.mL, as the LD was stimulated to contract. When the optimized parameters were used, the TtTI decreased by 45%, from 11.2 to 6.2 mm Hg.s, and the PtVA by 33%, from 1984 to 1371 mm Hg.mL. CONCLUSIONS: Our results suggest that DCM with a fluid-filled balloon decreases MVo2 as the LD contracts and that LD stimulation parameters have a determining effect on this benefit.

New technique measures decreased transmural myocardial pressure in cardiomyoplasty.

BACKGROUND: We introduce the use of a fluid-filled balloon, interposed between myocardium and latissimus dorsi (LD), as a new technique to measure transmural myocardial pressure in an acute goat model of dynamic cardiomyoplasty. METHODS: A half-ellipsoidal balloon, composed of polychloryl vinyl layers, was sutured to the atrioventricular groove in 5 goats, thereby completely enveloping both ventricles. Left LD dynamic cardiomyoplasty was then performed, anchoring the LD to the felt sewing skirt of the balloon so that the LD completely covered the balloon. Left ventricular pressure and balloon pressure were measured with the stimulator in the 1:2 mode as balloon volume was varied. RESULTS: Average transmural myocardial pressure, defined as left ventricular pressure minus balloon pressure, decreased from 34.4 mm Hg to 15.6 mm Hg during stimulator-on beats (p < 0.05). CONCLUSION: These results support the conclusion that dynamic cardiomyoplasty unloads the left ventricle by decreasing wall stress. Furthermore, transmural myocardial pressure decreased more when balloon volume was increased, implying that the LD sarcomere length has an effect on wall stress. A balloon may therefore allow optimization of LD sarcomere length and thus assisted cardiac performance.

Recovery and viability of an acute myocardial infarct after transmyocardial laser revascularization.

OBJECTIVES: The short- and long-term effectiveness of transmyocardial laser revascularization was evaluated in the setting of an acute myocardial infarction. BACKGROUND: Theoretically, transmyocardial laser revascularization allows direct perfusion of the ischemic area as ventricular blood flows through the channels to the myocardium. METHODS: Infarcts were created by coronary occlusion in 30 sheep. Eighteen of these sheep were studied to assess short-term efficacy. The infarct was reperfused after 1 h by either removing the occlusion or by laser drilling using a high power carbon dioxide laser. The occlusions were left in place for the control group. To monitor regional recovery, percent systolic shortening was measured. To evaluate long-term effectiveness, 12 additional sheep underwent creation of an infarct. Six were treated with the laser, and six were untreated. The animals were restudied 30 days later. RESULTS: In the short-term experiment, the control and reperfusion groups exhibited no recovery of regional contractility. The laser group demonstrated improvement throughout the recovery period. There was a significant difference in the area of necrosis within the same area at risk (reperfusion group 44 +/- 6% and control group 39 +/- 5% vs. laser group 6 +/- 2%). After 30 days, none of the control animals showed evidence of contraction in the infarct, whereas the laser-treated animals did. Histologic analysis of the laser-treated infarcts revealed patent channels surrounded by viable myocardium. The control-group infarcts were necrotic and scarred. CONCLUSIONS: On the basis of both short- and long-term improved contractility, as well as diminished necrosis in the area at risk, these results indicate that transmyocardial laser revascularization may be an alternative method of treating ischemic heart disease.

Right latissimus dorsi cardiomyoplasty improves left ventricular function by increasing peak systolic elastance (Emax).

BACKGROUND: Dynamic cardiomyoplasty remains a promising but poorly understood surgical modality for selected patients with dilated cardiomyopathy. Despite encouraging clinical results, objective evidence of enhanced ventricular function using traditional indexes (cardiac output, ejection fraction, and dP/dt) has been difficult to document after cardiomyoplasty. Several investigators have suggested that cardiomyoplasty acts partly by unloading the left ventricle. These indexes all depend somewhat on loading conditions, however, and might not detect such an interaction. The time-varying elastance model provides an index of contractility, Emax, that is relatively insensitive to changes in loading conditions. We applied this model to study the effect of right latissimus dorsi cardiomyoplasty on left ventricular function in an acute canine model. METHODS AND RESULTS: Five dogs underwent acute cardiomyoplasty using untrained right latissimus dorsi muscle. Instrumentation included Millar pressure transducers in the left ventricle and aortic root, an electromagnetic flow probe around the ascending aorta, and a volume conductance catheter in the left ventricle. A cuffed nerve electrode around the thoracodorsal nerve and a right ventricular sensing lead were connected to a Medtronic Cardiomyostimulator (5 V, 30 Hz, 1:1 synchronization). Transient caval occlusions were performed with the stimulator both off and on to calculate Emax and the slope of the end-systolic pressure-volume relationship (Ees). Turning the stimulator on significantly increased peak systolic elastance (Emax) and end-systolic elastance (Ees) in all five dogs by an average of 56% and 78%, respectively (P < .05). End-diastolic volume and end-systolic volume decreased by 18% and 28%, respectively (P < .05). All other measured hemodynamic parameters, including peak left ventricular pressure, mean arterial pressure, cardiac output, stroke volume, stroke work, ejection fraction, preload-recruitable stroke work, and dP/dt, did not change significantly. CONCLUSIONS: These results show that, in this acute canine model, right latissimus dorsi cardiomyoplasty significantly improves left ventricular function while decreasing left ventricular volumes. The results are consistent with the theory that cardiomyoplasty increases contractility while unloading the ventricle by decreasing end-diastolic volume. This increase in Emax despite inconsistent changes in other indexes underlies the importance of using load-insensitive indexes of ventricular function when studying cardiomyoplasty.

Prevention of complement-induced pulmonary hypertension and improvement of right ventricular function by selective thromboxane receptor antagonism.

The effect of complement activation on the pulmonary vascular system and on right ventricular function was studied in sheep (n = 12) by injection of cobra venom factor. Animals were instrumented for measurement of pulmonary flow, mean pulmonary artery pressure, right ventricular stroke work, arterial blood gases, and systemic vascular resistance. Blood was sampled from the left atrium and pulmonary artery to measure thromboxane B2, the metabolite of thromboxane A2, by radioimmunoassay. After baseline measurements, animals were randomly assigned to receive a selective thromboxane receptor antagonist SQ30741 as a 10 mg/kg bolus with an infusion of 10 mg/kg per hour or else to receive vehicle. Cobra venom factor was then injected (30 U/kg) in all animals, and data were recorded at 15, 30, 60, 90, and 120 minutes. In control animals there was a 2.4-fold increase in mean pulmonary artery pressure and a 76% increase in right ventricular stroke work at 15 minutes from baseline (p < 0.05); these values remained elevated for 30 minutes and returned to baseline by 1 hour with no change in systemic vascular resistance. Arterial oxygenation decreased by 124% at 15 minutes and remained depressed through the experiment, but in treated animals oxygen tension remained unchanged from baseline. Thromboxane B2 increased 95% from baseline in the control group and 1.5 fold in treated animals and followed a similar time course as the functional measurements (p < 0.05). A pulmonary vascular thromboxane B2 gradient of approximately 1000 pg/ml was measured at 15 and 30 minutes in both control and treated groups. (p < 0.05) We conclude that after complement activation in this model pulmonary hypertension and decreased oxygen tension are mediated by thromboxane release from the pulmonary vascular bed. This increased afterload causes a stress on the right ventricle as demonstrated by the increased right ventricular stroke work. Selective thromboxane receptor antagonism may be a beneficial therapy for pulmonary hypertension in patients after cardiopulmonary bypass.

Cardiac-derived thromboxane A2. An initiating mediator of reperfusion injury?

After crystalloid cardioplegic arrest, cardiac-derived thromboxane A2 may be an important initiating mediator of no-reflow and hemodynamic deterioration during reperfusion because of its potent vasoactive properties. Although previous studies have already documented the increased release of cardiac thromboxane A2 after ischemia, none have studied the effects of cardiac thromboxane A2 on hemodynamics. We therefore tested the ability of cardiac thromboxane A2 to mediate deterioration of coronary flow and functional recovery during reperfusion after global ischemia. Crystalloid-perfused rat hearts that had undergone Langendorff preparation (n = 30) were subjected to 2 hours of global ischemia at 15 degrees C under cardioplegic protection with (n = 15) or without (n = 15) thromboxane A2 receptor antagonist SQ29548. In eight of 15 hearts in each group, preischemic and postischemic aortic flow, coronary flow, cardiac output, heart rate, and stroke work were determined. In the remaining seven hearts in each group, preischemic and postischemic coronary effluent levels of the stable hydrolysis product of thromboxane A2 and thromboxane B2 were determined with radioimmunoassay through the use of nonrecirculating perfusate. At the completion of the experiment, water content was determined by wet weight/dry weight calculations. In a separate group (n = 7) preischemic myocardial water content was determined. Within the group protected by cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly decreased (p < 0.05) compared with preischemic values (aortic flow, 50.8 +/- 2.7 versus 29.4 +/- 3.3 ml/min; coronary flow, 13.2 +/- 1.3 versus 8.5 +/- 1.3 ml/min; cardiac output, 64.0 +/- 3.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.5 +/- 0.7 versus 7.1 +/- 0.8 cm H2O.ml). In relation to the group with cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly greater (p < 0.05) in the group with the receptor antagonist (aortic flow: 49.5 +/- 2.4 versus 29.4 +/- 3.3 ml/min; coronary flow; 12.4 +/- 1.2 versus 8.5 +/- 1.3 ml/min; cardiac output, 62.0 +/- 2.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.6 +/- 0.8 versus 7.1 +/- 0.8 cm H2O.ml). Overall, postischemic coronary effluent thromboxane B2 levels were greater than preischemic values (105.6 +/- 12.4 versus 69.6 +/- 9.8, p < 0.05) and treatment with the receptor antagonist did not significantly affect postischemic thromboxane B2 levels (92.0 +/- 7.3 versus 82.3 +/- 15.5, p = not significant). Neither ischemia nor treatment with the receptor antagonist significantly affected heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Improved recovery of heart transplants by combined use of oxygen-derived free radical scavengers and energy enhancement.

Oxygen free radical injury during reperfusion of ischemically stored heart transplants may further impair the ability of the transplanted heart to reuse substrate for recovery. We compared the effects of oxygen free radical scavengers, superoxide dismutase and catalase, either alone or combined with glucose-insulin-potassium, in an improved model of the heterotopically transplanted rat heart. Group 1 hearts (n = 8) received no preservation before transplantation and were transplanted immediately. Hearts in four other groups (n = 8 for each group) underwent cold storage (4 degrees to 6 degrees C) for 3 1/2 hours before transplantation. Five minutes before reperfusion of the transplanted hearts, recipient rats received one of the following intravenous treatments: saline (group 2), glucose-insulin-potassium (group 3), superoxide dismutase/catalase (group 4), and superoxide dismutase/catalase plus glucose-insulin-potassium (group 5). Left ventricular end-diastolic pressure, rate of rise of left ventricular pressure, myocardial blood flow, coronary resistance, and tissue adenosine triphosphate content of the heart transplants were assessed during or at the end of 2 hours of reperfusion. Hearts treated with superoxide dismutase/catalase alone showed improvement of end-diastolic pressure and myocardial blood flow. The use of glucose-insulin-potassium alone did not facilitate the recovery of transplanted hearts. In contrast, the combined use of superoxide dismutase/catalase plus glucose-insulin-potassium resulted in a superior recovery of all functional and hemodynamic parameters. These results indicate that free radical scavengers in the presence of glucose-insulin-potassium significantly improve functional recovery in the setting of heart transplantation.

Bench coronary angiography: a potentially useful method to assess coronary artery disease in the older donor heart without catheterization laboratory angiography.

To assess the diagnostic accuracy of ex vivo coronary artery arteriography, 12 sheep hearts were harvested, after random multiple coronary occlusions were created. The hearts were radiographed either in the flat (n = 6) or upright suspended (n = 6) position with the aorta cross-clamped. The aortic root was cannulated with an 18-gauge needle and flushed with cold normal saline solution. Five milliliters of iodinated contrast media was injected under constant hand pressure, and angiographic views were taken with a conventional, portable x-ray machine. The aortic root was then immediately flushed with normal saline solution under constant pressure to minimize contrast contact with the vascular endothelium. Total elapsed time including film development was 7 to 10 minutes. In hearts that were radiographed lying flat, a ventriculogram was obtained because of aortic incompetence. In hearts suspended in the upright position, normal coronary anatomy and previously placed coronary occlusions were easily detected in every heart that was read blindly by angiographers. To assess the effects of the contrast media on ventricular performance, five rabbit hearts were harvested and mounted on a Langendorff apparatus for functional analysis at controlled left ventricle volumes. Diastolic and systolic left ventricular pressures were unaffected by the dye injection. This simple and rapid method to evaluate coronary anatomy of the donor heart could be potentially useful in the assessment of older donor hearts in the operating room, thus increasing the volume of donor hearts available for transplantation.

Improved distribution of antegrade cardioplegic solution with simultaneous coronary sinus occlusion following acute coronary artery occlusion.

This study was designed to evaluate the distribution of cardioplegic solution infused antegradely with simultaneous coronary sinus occlusion. After 1 hr LAD occlusion, sheep were placed on cardiopulmonary bypass. Hearts were arrested with 300 ml of cold cardioplegia and replenished with two additional doses. In group I (n = 10), antegrade cardioplegia (ACP) was given alone; in group II (n = 9), ACP was given in combination with simultaneous coronary sinus occlusion. Microspheres were infused into the cardioplegic line to determine the antegrade distribution of the solution, while a different microsphere was injected into the anterior interventricular vein to detect the venous backflow of the solution. The data showed that myocardium distal to LAD occlusion in group II received more antegrade (0.17 +/- 0.02 versus 0.06 +/- 0.02 ml/g/min, P less than 0.01, in subendocardium; and 0.15 +/- 0.03 versus 0.09 +/- 0.02 ml/g/min, P = NS, in subepicardium) and retrograde (2181 +/- 455 versus 0 counts/g/min, P less than 0.01, in subendocardium; and 2,146 +/- 527 versus 0 counts/g/min, P less than 0.01, in subepicardium) distribution of cardioplegic solution in comparison to group I. We therefore conclude that simultaneous coronary sinus occlusion significantly improves the distribution of antegrade cardioplegic solution to the regionally occluded myocardium by increasing collateral flow as well as venous backflow.

Controlled reperfusion of the regionally ischemic myocardium with leukocyte-depleted blood reduces stunning, the no-reflow phenomenon, and infarct size.

Open-chest sheep underwent 90 minutes' occlusion of the diagonal branch of the left anterior descending coronary artery, followed by vented cardiopulmonary bypass. After 30 minutes of cardioplegic arrest, simulating distal anastomoses, the occlusion on the coronary artery branch was released. Controlled reperfusion (40 to 50 mm Hg, 135 to 150 ml/min) for the first 20 minutes was delivered at the aortic root with either unmodified whole blood (control, n = 7) or blood passed through leukocyte filters (filters, n = 7). Serial measurements were made during 3 additional hours reperfusion off cardiopulmonary bypass. During ischemia, the major determinants of infarct size, which include area at risk, collateral myocardial blood flow, and rate-pressure product were not significantly different between groups. Overall, during reperfusion, mean left ventricular stroke work index in the filter group was greater than in the control group (28.7 +/- 5.8 versus 12.6 +/- 6.4 x 10(3) erg/gm, p less than 0.05), as was mean rate of rise of left ventricular pressure (1900 +/- 260 versus 1348 +/- 279 mm Hg/sec, p less than 0.05). Myocardial blood flow to the area at risk at 3 1/2 hours of reperfusion in the filter group was also significantly better than in the control group (0.57 +/- 0.15 versus 0.27 +/- 0.05 ml/min/gm, p less than 0.05), as was necrotic area as a percentage of area at risk (40% +/- 6% versus 70% +/- 5%, p less than 0.05). These results demonstrate amelioration of myocardial stunning and the no-reflow phenomenon, as well as decreased infarct size. We conclude that controlled reperfusion with leukocyte-depleted blood is superior to whole-blood reperfusion for the surgical treatment of acute regional ischemia.