Initial Canadian experience with artificial blood (Fluosol-DA-20%) in severely anemic patients.

Fluosol-DA-20% (FDA), a synthetic perfluorocarbon emulsion with oxygen (O2) carrying capability, has recently become available in North America for clinical trials in severely anemic patients. Three patients have so far received FDA at our institution. All were severely anemic (Hct's 12-15%), and were administered FDA in anticipation of perioperative blood loss. Observations made in these patients indicate that: FDA can act as a plasma expander; no firm conclusions can be made as to whether FDA increases O2 consumption in the absence of directly measured arterial and mixed-venous O2 contents; mixed-venous oxyhemoglobin saturation at high FiO2 increases following FDA administration because a significant proportion of the consumed O2 (24-37% in our patients at FiO2 = 1.0) is transported by FDA; hemodynamic reactions to a test dose of FDA may occur, and may be serious enough to preclude further FDA administration; and technical recommendations for the administration of FDA should include the use of direct arterial and mixed-venous O2-content determinations, and continuous spectrophotometric mixed-venous oxyhemoglobin saturation monitoring.

Protection of the hypertrophied pig myocardium. A comparison of crystalloid, blood, and Fluosol-DA cardioplegia during prolonged aortic clamping.

The myocardial protective effects of crystalloid, blood, and Fluosol-DA-20% cardioplegia were compared by subjecting hypertrophied pig hearts to 3 hours of hypothermic (10 degrees to 15 degrees C), hyperkalemic (20 mEq/L) cardioplegic arrest and 1 hour of normothermic reperfusion. Left ventricular hypertrophy was created in piglets by banding of the ascending aorta, with increase of the left ventricular weight-body weight ratio from 3.01 +/- 0.2 gm/kg (control adult pigs) to 5.50 +/- 0.2 gm/kg (p less than 0.001). An in vivo isolated heart preparation was established in 39 grown banded pigs, which were divided into three groups to receive aerated crystalloid (oxygen tension 141 +/- 4 mm Hg), oxygenated blood (oxygen tension 584 +/- 41 mm Hg), or oxygenated Fluosol-DA-20% (oxygen tension 586 +/- 25 mm Hg) cardioplegic solutions. The use of crystalloid cardioplegia was associated with the following: a low cardioplegia-coronary sinus oxygen content difference (0.6 +/- 0.1 vol%), progressive depletion of myocardial creatine phosphate and adenosine triphosphate during cardioplegic arrest, minimal recovery of developed pressure (16% +/- 8%) and its first derivative (12% +/- 7%), and marked structural deterioration during reperfusion. Enhanced oxygen uptake during cardioplegic infusions was observed with blood cardioplegia (5.0 +/- 0.3 vol%), along with excellent preservation of high-energy phosphate stores and significantly improved postischemic left ventricular performance (developed pressure, 54% +/- 4%; first derivative of left ventricular pressure, 50% +/- 5%). The best results were obtained with Fluosol-DA-20% cardioplegia. This produced a high cardioplegia-coronary sinus oxygen content difference (5.8 +/- 0.1 vol%), effectively sustained myocardial creatine phosphate and adenosine triphosphate concentrations during the extended interval of arrest, and ensured the greatest hemodynamic recovery (developed pressure, 81% +/- 6%, first derivative of left ventricular pressure, 80% +/- 10%) and the least adverse morphologic alterations during reperfusion. It is concluded that oxygenated Fluosol-DA-20% cardioplegia is superior to oxygenated blood and especially aerated crystalloid cardioplegia in protecting the hypertrophied pig myocardium during prolonged aortic clamping.

The role of intimal hyperplasia in arterial spasm.

It has been postulated that even moderate spasm in an artery with intimal hyperplasia can produce organ hypoxia because there is an excessive reduction in the diameter of the lumen. To test this hypothesis we created intimal hyperplasia in one femoral artery in five pigs and then induced arterial spasm by administering ergonovine maleate. Arterial spasm did not produce a greater reduction in the luminal diameter of the femoral artery with intimal hyperplasia than it did in the normal femoral artery. Until further evidence appears this hypothesis must be viewed with caution.

Toward a better understanding of the hemodynamic effects of protamine and heparin interaction.

Hemodynamic changes have been documented during protamine infusion into heparinized but not unheparinized pigs and suggest that a protamine-heparin interaction might be responsible. This hypothesis was tested in four groups of pigs by varying the dosage and order of administration of these two drugs: Group I (n = 9) received heparin (3 mg/kg) followed by protamine (3 mg/kg); Group II (n = 9) received protamine (3 mg/kg) followed by heparin (3 mg/kg); Group III (n = 9) received protamine (25 mg/kg) followed by heparin (3 mg/kg); and Group IV (n = 16) received protamine-heparin complex (protamine 3 mg/kg and heparin 3 mg/kg mixed immediately prior to injection). Systemic and pulmonary arterial pressures, systemic and pulmonary vascular resistances, left ventricular end-diastolic pressure, central venous pressure, cardiac output, and heart rate were measured before and at 1.0, 2.5, 5.0, and 15 minutes after protamine, heparin, or protamine-heparin complex infusions. Immediately following protamine infusion, Group I pigs exhibited transiently but significantly increased pulmonary artery pressure, pulmonary vascular resistance, systemic vascular resistance, and central venous pressure and decreased cardiac output with (Group Ib, n = 5) or without (Group Ia, n = 4) systemic hypotension. The fact that no hemodynamic changes occurred in Group II confirms that infusion of clinical doses of protamine produces no hemodynamic changes in unheparinized pigs. Protamine alone in high doses (Group III) produced hemodynamic changes similar to clinical-dose protamine reversal of heparin (Group I). This effect suggests that the presence of heparin in the circulation lowers the threshold for protamine-mediated hemodynamic responses. Infusion of heparin (3 mg/kg) into pigs 15 minutes after treatment with high (25 mg/kg) (Group III) but not clinical (3 mg/kg) (Group II) doses of protamine produced hemodynamic effects similar to clinical-dose protamine reversal of heparin (Group I), suggesting that a protamine-heparin interaction may be responsible. These results also suggest a rapid inactivation in vivo of clinical doses (3 mg/kg) (Group II) of infused protamine. Protamine-heparin complex formed in vitro (Group IV) also produced hemodynamic changes similar to clinical-dose protamine reversal of heparin (Group I), suggesting that formation of this complex in vivo may be the protamine-heparin interaction responsible. Protamine-heparin complex may well be a useful tool in further elucidating the full effects of protamine reversal of heparin.

Recurrent or residual shunt following repair of acute postinfarctional ventricular septal defect.

Recurrent or residual ventricular septal defect following operative repair of postmyocardial infarction ventricular septal defect has been reported in many series. Most commonly, this is noted incidentally on postoperative cardiac catheterization or as a murmur in relatively asymptomatic patients in whom no further operation is required. Less frequently, its onset is a catastrophic event leading to the patient's death. On the other hand, the shunt may be sufficiently small to allow time for reoperation. With recent improvement in surgical techniques, more patients with this complication of myocardial infarction have been saved. Recurrent or residual ventricular septal defects have become less frequent, decreasing from a rate of 46% before 1970 to an overall 15% today. Few details have been published about recurrence or persistence of ventricular septal defect following operative repair. The authors report on a patient with a persistent ventricular septal defect following operation and necessitating reoperation. They describe the operative repair and review of the literature on this condition since 1973.

Reaction of subcutaneous tissues to injection of Fluosol-DA, 20%.

To study the extent of tissue reaction, the blood substitute Fluosol-DA, 20%, blood, normal saline and doxorubicin (Adriamycin) were injected in equal amounts into the subcutaneous tissues of four separate regions of the dorsum of seven rats. The animals were sacrificed at 6, 12, 24 and 48 hours, and at 1, 2 and 6 weeks after injection. The injected areas were examined by light and electron microscopy and the reaction was graded semiquantitatively. Results indicated the following: (a) saline, as expected, produced only mild inflammation that quickly resolved; (b) blood caused a hematoma with recognizable erythrocytes for 7 days and by 14 days hemosiderin-laden macrophages and fibrosis were present; (c) Adriamycin caused necrotizing lesions that were delayed for 24 hours, were severe at 2 and 7 days, and caused the disappearance of the muscle layer by 14 days and (d) Fluosol-DA caused the appearance of foamy macrophages at 12 hours that persisted until at least 2 weeks after injection. The authors conclude that Fluosol-DA, 20%, is not inert and causes a characteristic inflammatory response when injected subcutaneously. Whether a clinically important problem from subcutaneous infiltration of Fluosol could arise, for example, around a peripheral intravenous catheter, has yet to be determined. At present, it is probably safer to administer this drug through a central vein.

Surgery for postinfarction left ventricular aneurysm: prognosis and long-term follow-up.

To identify preoperative indicators of outcome following surgery for postinfarction left ventricular aneurysm, the authors have analysed the clinical course of 67 consecutive patients who underwent operation from 1970 to 1982. Follow-up extended to 12 years (mean 4.6 years) and was 97% complete. Postoperative mortality was 8.9%. Factors that were associated with a significantly (p less than 0.05) increased risk of early death included emergency surgery, the presence of ventricular arrhythmias preoperatively and a left ventricular end-diastolic pressure of more than 25 mm Hg on cardiac catheterization. Patients who underwent myocardial revascularization concomitantly had a lower mortality (7.1% v. 18.2% for aneurysmectomy alone), decreased postoperative morbidity and increased longevity. Marked functional improvement was noted in all groups. Actuarial survival (including operative mortality) was 66% at 6 years, and was significantly (p less than 0.05) better in patients operated upon for angina (83.6% +/- 8.1%) than in those operated upon for congestive heart failure (53% +/- 13%). The authors conclude that the most important predictor of outcome following postinfarction aneurysm surgery is the preoperative hemodynamic status of the left ventricle. Since functional recovery and prognosis after operation have been excellent, an aggressive surgical approach to symptomatic left ventricular aneurysms is warranted.

Differential electrical activity of the atria during cardioplegic arrest in pigs.

To elucidate the electrical interrelationship of the atria during cardioplegic arrest, simultaneous bipolar right atrial (RA) and left atrial (LA) electrograms and myocardial temperatures of all four chambers of the heart were recorded in 10 pigs during an hour of aortic clamping. Five pigs (Group 1) underwent single venous cannulation; in 5 others (Group 2), snared double caval cannulation, RA venting, and intracavitary RA irrigation with cold saline solution were employed. Myocardial protection was provided by systemic hypothermia (28 degrees C) and intermittent intraaortic administration of cold (4 degrees C) hyperkalemic (20 mEq/L) crystalloid cardioplegic solution. Single RA cannulation was associated with sustained RA activity during cardioplegic arrest and with the warmest mean myocardial temperatures. Electrical activity was infrequent in the left atrium, which was often silent while RA impulses continued to be observed. Four Group 1 pigs exhibited high-grade RA-LA block, whereas in 2 animals completely asynchronous RA-LA electrical activity occurred. Isolated LA activity was not encountered. The combined methods used in Group 2 pigs significantly reduced mean myocardial temperatures. Both RA and LA impulses were practically abolished, and their mean durations decreased 96% and 85%, respectively. It is concluded that the pattern of electrical activity differs in the two atria during cardioplegic arrest when a single venous cannula is employed. Intracavitary RA irrigation with cold saline solution in the presence of snared caval cannulas provides improved myocardial hypothermia and effectively eliminates both RA and LA activity in the course of cold crystalloid cardioplegia.

Atrial electrical activity and its suppression during cardioplegic arrest in pigs.

Right atrial electrical activity and myocardial temperatures of all four chambers were monitored during a 1 hour period of cardioplegic arrest in 20 pigs subjected to different methods of venous cannulation and cardiac cooling. Myocardial protection was provided by systemic hypothermia (28 degrees C) and intermittent intra-aortic administration of cold (4 degrees C) hyperkalemic (20 mEq/L) crystalloid cardioplegia. The use of a single right atrial cannula for venous drainage was associated with sustained atrial activity (50 +/- 5.5 minutes) during cardioplegic arrest and the warmest right atrial (27 degrees +/- 0.2 degrees C) and right ventricular (20.5 degrees +/- 0.4 degrees C) temperatures. Separate caval cannulation with snaring and right atrial venting decreased right atrial and ventricular temperatures marginally (25.3 degrees +/- 0.5 degrees C and 19.1 degrees +/- 0.4 degrees C, respectively, p less than 0.05) but did not significantly alter the duration of atrial electrical activity (42.2 +/- 2.5 minutes, p greater than 0.05). Addition of an extracavitary right atrial drip of cold (4 degrees C) saline, 750 ml for the 1 hour aortic clamping period, reduced right atrial temperature (22.8 degrees +/- 0.4 degrees C) and activity (24.8 +/- 6.3 minutes) to a significant extent. Intracavitary irrigation of the right atrium with cold saline, in the presence of snared double caval cannulas, decreased right atrial and ventricular temperatures most dramatically (17.0 degrees +/- 0.5 degrees C and 17.5 degrees +/- 0.3 degrees C, respectively, p less than 0.05), reduced the duration of atrial electrical activity by 84% (to 8 +/- 3.9 minutes, p less than 0.01), and diminished the total number of atrial contractions per hour of aortic clamping by 88%. It is concluded that intracavitary right atrial cooling with separate snared caval cannulation is the most effective method of ensuring atrial inactivity and prolonged right heart hypothermia during cardioplegic arrest.

Spontaneous ventricular fibrillation occurring immediately after institution of cardiopulmonary bypass: possible clinical implications.

Twenty-four patients developed spontaneous ventricular fibrillation (SVF), for no apparent reasons, immediately after the institution of cardiopulmonary bypass (CPB) and prior to aortic cross-clamping and cardioplegic arrest. These were compared to 76 similar patients who remained in normal sinus rhythm (NSR). The following observations were made: (1) SVF occurred more frequently in patients undergoing urgent coronary bypass and having unstable or crescendo angina with severe triple coronary artery disease and/or left main coronary artery stenosis; (2) in nonvented hearts the mean left atrial pressure increased to levels above 28 mm Hg during SVF and prior to cardioplegic arrest; (3) at the end of CPB, arrhythmias and episodes of ventricular fibrillation were common (48% SVF versus 8% NSR); (4) the overall myocardial infarction rate was 37% SVF versus 4% NSR; and (5) the mortality rates were 25% SVF versus 1.3% NSR. It is postulated that the occurrence of SVF at the start of CPB may be indicative of serious derangements in myocardial cellular metabolism and/or function and may have clinical and prognostic implications.