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This phase I open label, dose-escalating study shows that gene transfer of vascular endothelial growth factor-2 naked deoxyribonucleic acid by direct myocardial injection by way of thoracotomy in patients with Canadian Cardiovascular Society class 3 or 4 angina is feasible and safe. The procedure is well tolerated, with few major adverse cardiac events at 1 year, and without complications directly related to gene expression. In this prospective, nonblinded study, the procedure is associated with clinical improvement; however, there was no angiographic evidence of angiogenesis and there is a great potential for a sham or placebo effect in the study patients. A randomized phase III trial is underway that will help determine the efficacy of vascular endothelial growth factor-2 gene transfer in “no-option” patients.

Tha pathophysiology of brain injury in patients undergoing cardiopulmonary bypass remains unclear despite several decades of inquiry. The advent of noninvasive high-resolution brain and cerebrovascular imaging by magnetic resonance, computed tomography, and pulsed Doppler ultrasonography now permits in vivo assessment of pathophysiological mechanisms. Neuroradiographic and carotid duplex studies were performed in patients who developed neurological deficits following cardiopulmonary bypass. Among 30 symptomatic patients undergoing magnetic resonance or computed tomography brain scans, 18 (60%) had findings of acute ischemic injury. Embolic infarction was evident in 14 (78%) of these 18 patients. Watershed injury was the predominant finding in a single patient, while findings consistent with global anoxia were present in another patient. Carotid atheroemboli were excluded as a possible source of embolism in 11 patients whose carotid duplex studies were unremarkable preoperatively as well as in 3 further patients whose neuroradiographic findings did not correspond with their moderate carotid disease. It is concluded that infarction due to noncarotid embolism is the primary pathophysiology of neurological deterioration following cardiopulmonary bypass.

Postoperative hemorrhage in patients undergoing open-heart surgery is a major cause of morbidity and mortality. Monitoring of coagulation in these patients has routinely involved the activated clotting time. Thromboelastography is currently used as a monitor of coagulation during liver transplantation. The thromboelastogram, by providing information on the interaction of all the coagulation precursors, gives more clinically useful information on coagulation than that available from the coagulation profile or the activated clotting time alone. This study was done to assess the usefulness of thromboelastography in open-heart surgery. Thirty-eight patients (29 undergoing coronary artery bypass grafting and 9 undergoing valve replacement) were studied with activated clotting time, thromboelastography, and coagulation profiles during three periods: before bypass, during bypass, and after protamine administration. Thromboelastography was a significantly better predictor (87% accuracy) of postoperative hemorrhage and need for reoperation than was the activated clotting time (30%) or coagulation profile (51%). Thromboelastography is easy to use and provides diagnostic data within 30 minutes of blood sampling.

Intra-aortic balloon counterpulsation (IABC) was developed to assist the circulation in pump failure. Its use has recently been suggested to decrease or retard the extent of ischemia in normotensive patients with acute myocardial infarction. In dogs, the combination of IABC and phenylephrine decreased the extent of ischemia after acute coronary occlusion by 76 per cent, far more than IABC alone. The data suggest that increasing coronary perfusion is a more important factor than decreasing left ventricular afterload in this effect of IABC.

With the use of an epicardial ST mapping technique, left ventricular bypass (LVB) was shown to reduce effectively the myocardial ischemia associated with coronary artery occlusion in dogs in proportion to the extent of bypass. Pulsatile flow was equally, but not more, effective. A reduction in cardiac work is proposed as the basis for these benefits.

The effects of intraaortic balloon counterpulsation (IABC) on the magnitude and severity of myocardial ischemic injury were studied in 19 dogs following acute coronary occlusion and in two patients with cardiogenic shock. In the experimental group, epicardial electrocardiograms were taken from 10-14 sites on the anterior surface of the left ventricle following occlusion of the left anterior descending coronary artery or its apical branch. The average S-T-segment elevation ([see Equation in PDF File]) was used as an index of the magnitude of myocardial ischemic injury. In six dogs, two successive 20-min occlusions were performed, and IABC was started prior to the second occlusion. [see Equation in PDF File] 15 min following occlusion decreased from 3.3 ± 0.9 mv after the control occlusion to 1.4 ± 0.4 mv ( P < 0.01) after the occlusion with IABC. In three dogs in which the occlusion was maintained and IABC initiated 30 min later, [see Equation in PDF File] decreased from 1.2 to 0.6 mv. In six dogs in which IABC was started 3 hours after occlusion, it induced a reduction of [see Equation in PDF File] from 4.2 ± 1.1 to 2.8 ± 1.0 mv ( P < 0.01). In four dogs, ischemic injury was augmented by isoproterenol infusion (0.25 µg/kg/min), and while continuing the infusion IABC was initiated. It reduced [see Equation in PDF File] from 8.0 ± 1.9 to 5.7 ± 1.8 mv ( P < 0.05). Thus, IABC reduced the magnitude and extent of myocardial ischemic injury after experimental coronary occlusion, both when IABC was employed prior to, and 3 hours following, coronary occlusion. IABC was also effective in reducing myocardial ischemic injury which had been increased by isoproterenol infusion. Employing a noninvasive technic, which utilizes 35 electrodes on the thorax, the effects of IABC were examined in two patients with cardiogenic shock associated with acute myocardial infarction. Preliminary observations in these patients confirmed the experimental results indicating that IABC reduced myocardial ischemic injury.

The production of prosthetic valve incompetence during atriotomy closure is among the operative maneuvers utilized to prevent air embolism in mitral valve replacement. The leaflets of a porcine bioprosthesis may be retracted safely and effectively, thereby producing temporary valve incompetence, by placing three polypropylene sutures through the valve orifice and around the sewing ring to encircle the leaflets. These traction sutures are easily pulled out through the atriotomy suture line after all air has been displaced from the heart. The technique has been effective, easily accomplished, and without complications.