Biomedical subjects

O W Isom

Publications and source records attributed to O W Isom.

At least 37 records · Page 2Linked to original sources

PubMed1998

Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion.

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, and transgene expression from adenovirus vectors can provide in vivo delivery of proteins. On the basis of this knowledge, we hypothesized that local administration of a replication-deficient adenovirus vector expressing complementary DNA for VEGF (AdVEGF) would induce collateral vessel formation in the setting of ischemia that could protect against subsequent acute vascular occlusion. METHODS: Hindlimb ischemia was induced in Sprague-Dawley rats by means of unilateral ligation of the common iliac artery immediately followed by administration of 4 x 10(9)-plaque-forming units VEGF, the control vector AdNull, or phosphate-buffered saline solution into the iliofemoral adipose tissue and thigh muscles. Untreated rats with common iliac ligation were used as an additional control group. RESULTS: Local VEGF expression was observed for 5 days in AdVEGF-treated rats but not in controls. Three weeks after ligation and vector administration, the ipsilateral femoral artery was ligated for a model of an acute vascular occlusion in the setting of preexisting ischemia. Blood flow to the ischemic hindlimb relative to the contralateral hindlimb evaluated with color microspheres demonstrated significantly increased blood flow in the AdVEGF-treated rats compared with each control group (p < 0.0001). Relative blood flow assessed by means of 99mTc-sestamibi radionuclide scans also demonstrated increased blood flow to the ligated hindlimb of AdVEGF-treated rats compared with each control group (p < 0.002). AdVEGF-treated rats also demonstrated increased vascularity in the ligated limb compared with each control group as assessed by means of angiography (p < 0.0001) and histologic quantification of blood vessels less than 80 microm diameter in local adipose tissue and capillaries per muscle fiber (p < 0.0002). AdVEGF treatment prevented a rise in femoral venous lactate femoral venous concentrations 1 hour after femoral artery ligation in control rats (p < 0.04). CONCLUSIONS: An adenovirus vector expressing VEGF complementary DNA is capable of stimulating an angiogenic response that protects against acute vascular occlusion in the setting of preexisting ischemia, suggesting that in vivo gene transfer of VEGF complementary DNA might be useful in prophylaxis of advancing arterial occlusive disease.

Adenoviridae↗

PubMed1997

Channel patency and neovascularization after transmyocardial revascularization using an excimer laser: results and comparisons to nonlased channels.

BACKGROUND: Transmyocardial revascularization (TMR) has emerged as a promising treatment for ischemic heart disease in patients who are not candidates for coronary bypass surgery or angioplasty. Controversy exists, however, as to whether the use of laser energy is critical for TMR channel patency. We therefore compared by histologic assessment the outcome of lased channels with nonlased channels 30) days after TMR, using a low energy, short-pulse, fiberoptic excimer laser. METHODS AND RESULTS: In each of six sheep, 36 1-mm TMR channels (9 mJ; 240 Hz; 1.55 cm advance/s) were placed in the anterior wall of the left ventricle, and 12 1-mm nonlased channels were created in adjacent segments by advancing the fiberoptic through the left ventricular wall with the laser inactivated. Of the 36 lased channels, 56+/-7.3% were identifiable, and 100% of those identifiable appeared to represent a "channel derivative" with evidence of an endothelialized lumen, whereas none of the nonlased channels had evidence of channel patency. Lased channels had a marked neovascular response (graded on a 0-3 scale) compared with nonlased channels (2.5+/-0.1 versus 1.0+/-0.1; P<.05). Echocardiography performed 1 and 30 days after TMR demonstrated normal global and regional left ventricular function in all animals. Creatinine phosphokinase myocardial band fractions were not significantly increased after TMR. CONCLUSIONS: TMR using the excimer laser results in increased evidence of channel derivatives and neovascularization compared with nonlased channels while preserving normal ventricular function. These findings suggest that laser energy may be an important component of TMR strategy.

Animals↗

PubMed1997

Impact of minimum hematocrit during cardiopulmonary bypass on mortality in patients undergoing coronary artery surgery.

BACKGROUND: The hematocrit on cardiopulmonary bypass (CPB) frequently falls to a low level during many cardiac surgical procedures. This study was designed to explore the impact on mortality of minimum hematocrit level achieved during the CPB after coronary artery surgery. METHODS AND RESULTS: Two thousand seven hundred thirty-eight sequential isolated coronary artery surgery patients during a 42-month period at a tertiary academic center were included in this study. Thirty-one standardized preoperative risk factors used in a multiple logistic regression revealed eight statistically significant independent predictors for postoperative mortality. Minimum hematocrit level during CPB was then added to the regression model and was found to be an independent risk factor for mortality. The entire patient population was divided into dichotomous groups using different minimum hematocrit levels on CPB for the determination of cutoff points by multiple logistic regression. After adjusting for other risk factors, the minimum hematocrit level of 14% was found to be a statistically significant cutoff point. Patients with minimum hematocrit levels < or =14% were found to have an increased probability of risk-adjusted mortality (odds ratio, 2.70; P=.002). A subgroup analysis revealed that high-risk patients with minimum hematocrit levels < or =17% were found to have a significantly increased probability of postoperative mortality (odds ratio, 2.20; P=.017). CONCLUSIONS: Minimum hematocrit level during CPB is an independent risk factor for mortality after coronary artery surgery. There is a significantly increased risk of mortality for hematocrit levels < or =14%. For high-risk patients, there is a significantly increased risk of mortality for hematocrit levels < or =17%.

Adult↗

PubMed1997

Regional angiogenesis induced in nonischemic tissue by an adenoviral vector expressing vascular endothelial growth factor.

The feasibility of a single administration of a replication-deficient adenovirus (Ad) vector encoding the cDNA for human vascular endothelial growth factor (VEGF) (AdCMV.VEGF) to induce neovascularization in vivo in normal tissue was evaluated in retroperitoneal adipose tissue. Following administration of AdCMV.VEGF (10(9) pfu/50 microliters), maximal VEGF cDNA expression was observed at 2-5 days in the injected adipose tissue. No VEGF protein was detected at > or = 10 days in injected adipose tissue, and there was no increase in serum VEGF levels at any time. In vivo quantification of the number of blood vessels using 30x visualization of the adipose tissue demonstrated an increase in vessel number by 10 days, plateauing by 30 days with a 123% increase in vessel number compared to the control vector AdCMV.Null, despite the fact that no VEGF protein was detected after 5 days. Consistent with the in vivo data, histologic quantification of capillary number demonstrated an increase by day 5, reaching a 38% increase over AdCMV.Null by day 30. These observations demonstrate that an Ad vector carrying the VEGF cDNA is capable of inducing the growth of new blood vessels in a regional fashion in a relatively avascular, normal organ. This suggests in vivo Ad-mediated gene transfer may be useful for therapeutic angiogenesis in the treatment of ischemic cardiovascular disease.

Abdomen↗

PubMed1997

Circumvention of anti-adenovirus neutralizing immunity by administration of an adenoviral vector of an alternate serotype.

Effective gene transfer and expression following repetitive administration of adenoviral (Ad) vectors in experimental animals is limited by anti-Ad neutralizing antibodies. Knowing that anti-Ad humoral immunity is serotype-specific, we hypothesized that anti-Ad neutralizing immunity could be circumvented using Ad vectors of different serotypes (Ad2, Ad5) within the same subgroup (C) to transfer and express beta-glucuronidase (beta glu) in the lung. Sprague-Dawley rats received an intratracheal administration of either Ad2 beta glu or Ad5 beta glu, and, 14 days later, repeat administration of either the same vector or a vector of a different serotype. Analysis of serum and bronchoalveolar lavage fluid following initial vector administration demonstrated systemic and local serotype-specific neutralizing antibodies. For both the Ad2 and Ad5 vectors, beta glu expression 24 hr following the second administration of the same serotype was < 30% of that of naive animals. In contrast, beta glu expression 24 hr following second administration of a different serotype Ad vector was similar to expression at 24 hr of naive animals receiving a single administration (Ad5 beta glu followed by Ad2 beta glu, as well as Ad2 beta glu followed by Ad5 beta glu; p > 0.2 both comparisons). Although the alternative serotype bypassed anti-Ad neutralizing immunity, persistence of expression was reduced compared to that following administration to naive animals. Compatible with this observation, systemic administration of the same vectors to C57B1/6 mice demonstrated induction of cytotoxic T lymphocytes directed against the beta glu transgene, as well as products of the Ad genome. Interestingly, intratracheal administration of vectors with different serotypes and different transgenes to rats resulted in longer expression (but still not normalized) compared to that achieved with vectors of different serotypes but the same transgene. These observations demonstrate that alternate use of Ad vectors from different serotypes within the same subgroup can circumvent anti-Ad humoral immunity to permit effective gene transfer after repeat administration, although the chronicity of expression is limited, likely by cellular immune process directed against both the transgene and viral gene products expressed by the vector.

Adenoviridae↗

PubMed1997

Impact of embolization during coronary artery bypass grafting on outcome and length of stay.

BACKGROUND: Transcranial Doppler ultrasonography detects emboli in most patients during coronary artery bypass grafting. However, the significance of these emboli has not yet been established. METHODS: We monitored 82 patients during coronary artery bypass grafting with this technique and related the numbers of emboli to the outcomes and length of hospital stay. RESULTS: We detected cerebral emboli in all patients. Patients with stroke (n = 4; 4.9%) had a mean of 449 emboli, as compared with 169 emboli in patients without stroke (n = 78) (p = 0.005). Patients with major cardiac complications (n = 7) had a mean of 392 emboli, as compared with 163 in patients without such complications (n = 75) (p = 0.003). The mean hospital stay of survivors was 8.6 days in patients with fewer than 100 emboli (n = 40), 13.5 days in patients with 101 to 300 emboli (n = 23), 16.3 days in those with 301 to 500 emboli (n = 16), and 55.8 days in patients with more than 500 emboli (n = 6) (p = 0.0007). This relation was unchanged when patients with complications were excluded. The correlation between embolization and outcome was independent of the extent of aortic atheroma or age. CONCLUSIONS: Emboli detected during coronary artery bypass grafting are significantly related to major cardiac and neurologic complications and affect length of stay in all patients, even in the absence of such specific complications.

Adult↗

PubMed1997

The history of surgery for ischemic heart disease.

Myocardial revascularization had its beginnings in the early 1900s with extracardiac operations, such as sympathetic denervation and thyroid ablation. From there it evolved through neovascularization via pericardial poudrage and cardiopexy in the 1930s to 1950s, to mammary artery myocardial implantation in the 1940s and endarterectomy in the 1950s, to saphenous vein- and mammary artery-coronary artery bypass grafting in the 1960s. The history of the surgical treatment of myocardial ischemia is presented here in chronologic sequence to highlight the prescient thinking and the persistence of efforts, as well as the false starts and the rediscovery of old ideas, that have marked the development of this treatment.

Animals↗

PubMed1997

Aortic atheroma is related to outcome but not numbers of emboli during coronary bypass.

BACKGROUND: The relation between aortic atheroma severity and stroke after coronary artery bypass grafting is established. The relation between atheroma severity and other outcome measures or numbers of emboli has not been determined. METHODS: Using transesophageal echocardiography, we determined the severity of atheroma in the ascending, arch, and descending aortic segments in 84 patients undergoing operations. Seventy patients were monitored using transcranial Doppler ultrasonography. RESULTS: The incidence of stroke was 33.3% among 9 patients with mobile plaque of the arch and 2.7% among 74 patients with nonmobile plaque (p = 0.011). Cardiac complications were not significantly related to atheroma severity in any aortic segment. Length of stay was significantly related to atheroma severity in the aortic arch (p = 0.025) and descending segment (p = 0.024). The presence of severe atheroma in both the arch and descending segments was associated with significantly longer hospital stays as compared with patients with severe atheroma in neither segment (p = 0.05). Numbers of emboli were greater in patients with severe atheroma at clamp placement, although the differences did not achieve statistical significance. CONCLUSIONS: Aortic atheroma severity is related to stroke and to the duration of hospitalization after coronary artery bypass grafting. The lack of correlation between numbers of emboli and atheroma severity suggests that m any emboli may be nonatheromatous in nature.

Adult↗

PubMed1997

Therapeutic angiogenesis: a comparative study of the angiogenic potential of acidic fibroblast growth factor and heparin.

PURPOSE: Acidic fibroblast growth factor (aFGF) is a potent mitogen for vascular and other mesenchymal cells in vitro that can induce angiogenesis in vivo. Although heparin has no mitogenic potential of its own, it is an important aFGF cofactor in vitro and may also be capable of stimulating angiogenesis. Because the development of a collateral vasculature in response to ischemia appears to be dependent on angiogenesis, we compared the abilities of aFGF with or without heparin and heparin alone to accelerate angiogenesis in a rat hind limb ischemia model. METHODS: Daily subcutaneous injections of saline solution (1 ml), heparin (0.05 mg), or human recombinant aFGF with or without heparin (1 microgram aFGF, 0.05 mg heparin) were administered into the hind limb region distal to the point of unilateral femoral artery ligation in the rat for the 10 days immediately after vascular occlusion. Angiogenicity was determined by histologic assessment of treatment outcomes. RESULTS: Histologic assessment of the number of vessels per microscopic field 10 days after vascular ligation in the fibrofatty tissues distal to the ligation point had the following results: saline solution, 10 +/- 4 vessels; heparin, 13 +/- 4 vessels (p < 0.05 vs saline solution); aFGF, 26 +/- 8 vessels; and aFGF/heparin 36 +/- 8 vessels (aFGF, aFGF/ heparin, p < 0.001 vs saline solution). Similar increases in vascularization were also noted in the skeletal muscle tissues distal to the vascular ligation point. Immunohistochemical analysis for the presence of proliferating cell nuclear antigen, a marker for mitogenic activity, demonstrated corresponding increases in proliferating cell nuclear antigen labeling for each of the treatment groups, expressed as a percentage of total vascular cell nuclei, as follows: saline solution, 7% +/- 2%; heparin, 21% +/- 8% (p < 0.05 vs saline solution); aFGF, 67% +/- 9%; and aFGF/heparin, 83% +/- 5% (aFGF, aFGF/heparin, p < 0.001 vs saline solution). CONCLUSIONS: The increased vascularization and mitogenic activity demonstrated by these respective studies suggest that angiogenesis is significantly accelerated by the administration of heparin alone and is accelerated to a greater extent by the administration of aFGF with or without heparin. The aFGF/heparin regimen may represent an optimal means of augmenting collateral vessel growth to relieve ischemia in the clinical setting.

Animals↗

PubMed1997

Open heart operations without transfusion using a multimodality blood conservation strategy in 50 Jehovah's Witness patients: implications for a "bloodless" surgical technique.

BACKGROUND: Blood transfusion persists as an important risk of open heart operations despite the recent introduction of a variety of new pharmacologic agents and blood conservation techniques as independent therapies. A comprehensive multimodality blood conservation program was developed to minimize this risk. STUDY DESIGN: To provide a strategy for operating without transfusion, this program was prospectively applied to 50 adult patients who are Jehovah's Witnesses and have undergone open heart operation at our institution since 1992. The blood conservation program used for these patients included the use of high-dose erythropoietin (800 U/kg load, 500 U/kg every other day), aprotinin (6 million U total dose full Hammersmith regimen), "maximal" volume intraoperative autologous blood donation, intraoperative cell salvage, continuous shed blood reinfusion, and drawing as few blood specimens as possible. RESULTS: Procedures performed included first-time coronary bypass operations (n = 30) and more complex operations, including reoperations, valve replacements, and multiple valve replacements with or without coronary bypass (n = 20). Despite the absence of transfusion, the mean discharge hematocrit in these patients was greater than 30 percent, and there was no anemia-related mortality rate in this group. The overall in-hospital mortality for the group was 4 percent. A subset analysis was performed between the 30 first-time coronary bypass patients (group 1) and a control group of 30 consecutive patients who were not Jehovah's Witnesses but had undergone first-time coronary bypass during the same period (group 2). The blood conservation program described in the previous paragraph was not used in group 2 patients and specific transfusion criteria were prospectively applied. The chest tube output in group 1 patients was less than 40 percent of that for group 2 patients at all points measured after operation (p < 0.01). Postoperative hematocrit levels in group 1 were greater than those for group 2, despite the absence of red blood cell transfusion and despite a significantly lower admission hematocrit and red blood cell mass in group 1. The average length of stay and ancillary costs for the two groups were equivalent. Although group 1 and 2 patients were well matched for preoperative transfusion risk factors, none of the group 1 patients required transfusion, but 17 (57 percent) group 2 patients met transfusion criteria and received 3.0 +/- 4.8 U (mean plus or minus standard deviation) of homologous blood or blood products. CONCLUSIONS: These results suggest that even complex open heart operations can be performed without homologous transfusion by optimally applying available blood conservation techniques. More generalized application of these measures may increasingly allow "bloodless" operations in all patients.

Adult↗

PubMed1996

Triiodothyronine therapy lowers the incidence of atrial fibrillation after cardiac operations.

BACKGROUND: Cardiopulmonary bypass results in a euthyroid sick state, and recent evidence suggests that perioperative triiodothyronine (T3) supplementation may have hemodynamic benefits. In light of the known effects of thyroid hormone on atrial electrophysiology, we investigated the effects of perioperative T3 supplementation on the incidence of postoperative arrhythmias. METHODS: One hundred forty-two patients with depressed left ventricular function (ejection fraction < 0.40) undergoing coronary artery bypass grafting were randomized to either T3 or placebo treatment groups in a prospective, double-blind fashion. Triiodothyronine was administered as a 0.8 micrograms/kg intravenous bolus at the time of aortic cross-clamp removal followed by an infusion of 0.113 micrograms.kg-1.h-1 for 6 hours. Patients were monitored for the development of arrhythmias during the first 5 postoperative days. RESULTS: The incidence of sinus tachycardia and ventricular arrhythmias were similar between groups. Triiodothyronine-treated patients had a lower incidence of atrial fibrillation (24% versus 46%; p = 0.009), and fewer required cardioversion (0 versus 6; p = 0.012) or anticoagulation (2 versus 10; p = 0.013) during hospitalization. Six patients in the T3 group versus 16 in the placebo group required antiarrhythmic therapy at discharge (p = 0.019). CONCLUSIONS: Perioperative T3 administration decreased the incidence and need for treatment of postoperative atrial fibrillation.

Adult↗

PubMed1996

Intraoperative autologous blood donation preserves red cell mass but does not decrease postoperative bleeding.

BACKGROUND: Postoperative bleeding and transfusion remain a source of morbidity and cost after open heart operations. The benefit of the acute removal and reinfusion of fresh autologous blood around the time of cardiopulmonary bypass-a technique known as intraoperative autologous donation (IAD)-has not been universally accepted. We sought to more clearly evaluate the effects of IAD on allogeneic transfusion and postoperative bleeding by removing, preserving, and reinfusing a calculated maximum volume of fresh autologous whole blood. METHODS: Ninety patients undergoing coronary artery bypass grafting or valvular operations were prospectively randomized to either have (IAD group) or not have (control group) calculated maximum volume IAD performed. Treatment was otherwise identical. Transfusion guidelines were uniformly applied to all patients. RESULTS: An average volume of 1,540 +/- 302 mL of fresh autologous blood was removed and reinfused in the IAD group. Postoperative hematocrits were significantly greater at 12 and 24 hours postoperatively in the IAD group versus the control group despite a significant decrease in both the percentage of patients in whom allogeneic red blood cells were transfused (17% versus 52%; p < 0.01) and the number of red blood cell units transfused per patient per group (0.28 +/- 0.66 and 1.14 +/- 1.19 units; p < 0.01). Conversely, chest tube output, incidence of excessive postoperative bleeding, postoperative prothrombin time, and platelet and coagulation factor transfusion requirement did not differ between groups. CONCLUSIONS: These results indicate that intraoperative autologous donation serves to preserve red blood cell mass. Its routine use in eligible patients is therefore justified. However, the removal and reinfusion of an individually calculated maximum volume of fresh autologous blood had no effect on postoperative bleeding or platelet and coagulation factor transfusion requirement. This lack of hemostatic effect belies the beliefs of many about the primary action of IAD, helps to delineate the optimal way in which to perform IAD, and carries implications regarding the use of allogeneic platelet and coagulation factors for the treatment of early postoperative bleeding.

Adult↗

PubMed1996

Direct in vivo gene transfer to canine myocardium using a replication-deficient adenovirus vector.

BACKGROUND: Direct myocardial gene transfer is a mordality that involves the introduction of genetic information into myocardial tissue to achieve a therapeutic effect. This study was designed to characterize the temporal and spatial limits of gene expression and to determine the safety of direct myocardial gene transfer in a large animal model using replication-deficient adenovirus vectors. METHODS: Mongrel dogs underwent left thoracotomy and direct myocardial injections (100 microL/injection) of adenovirus vectors (10(9) pfu) carrying the DNA for the reporter enzyme chloramphenicol acetyl transferase or the angiogenic protein vascular endothelial growth factor. Two to 14 days after vector administration, regional protein expression was evaluated in myocardium and distant organs. Left ventricular function, assessed by echocardiography, and routine hematologic and biochemical indices were evaluated before and after vector administration. RESULTS: Peak levels of chloramphenicol acetyl transferase activity were detected 2 days after vector administration, and levels above baseline persisted for at least 14 days. Local chloramphenicol acetyl transferase activity was detected at distances at least as far as 1.5 cm from the site of injection. Chloramphenicol acetyl transferase activity in distant organs was less than 0.1% of that in injected myocardium 7 days after vector administration. Localized expression of vascular endothelial growth factor was achieved for up to 7 days after a single vector administration. Cardiac function and laboratory values were unchanged during the study. CONCLUSIONS: Adenovirus-mediated direct myocardial gene transfer can be accomplished safely in a large animal model, providing high levels of protein expression in a greater spatial distribution than previously reported, with minimal transfection of distant organs. Sustained and localized expression of a potent angiogenic mediator has been accomplished, which may provide an innovative strategy to stimulate angiogenesis in ischemic myocardium.

Adenoviridae↗

PubMed1996

Cardiopulmonary bypass procedures in patients with cold-reactive hemagglutination. A case report and a literature review.

The use of hypothermia during cardiopulmonary bypass and cardioplegia poses a special problem in patients with cold-reactive hemagglutination. This is a case report of a successful aortic valve replacement on a patient with severe aortic valve stenosis and severely symptomatic cold agglutinin induced hemolytic anemia. This case illustrates the various problems in the perioperative management of these patients. A literature review of these rare cases is provided.

Aged↗

PubMed1995

Thyroid hormone treatment after coronary-artery bypass surgery.

BACKGROUND: Thyroid hormone has many effects on the cardiovascular system. During and after cardiopulmonary bypass, serum triiodothyronine concentrations decline transiently, which may contribute to postoperative hemodynamic dysfunction. We investigated whether the perioperative administration of triiodothyronine (liothyronine sodium) enhances cardiovascular performance in high-risk patients undergoing coronary-artery bypass surgery. METHODS: We administered triiodothyronine or placebo to 142 patients with coronary artery disease and depressed left ventricular function. The hormone was administered as an intravenous bolus of 0.8 microgram per kilogram of body weight when the aortic cross-clamp was removed after the completion of bypass surgery and then as an infusion of 0.113 microgram per kilogram per hour for six hours. Clinical and hemodynamic responses were serially recorded, as was any need for inotropic or vasodilator drugs. RESULTS: The patients' preoperative serum triiodothyronine concentrations were normal (mean [+/- SD] value, 81 +/- 22 ng per deciliter [1.2 +/- 0.3 nmol per liter]), and they decreased by 40 percent (P < 0.001) 30 minutes after the onset of cardiopulmonary bypass. The concentrations in patients given intravenous triiodothyronine became supranormal and were significantly higher than those in patients given placebo (P < 0.001). However, the concentrations were once again similar in the two groups 24 hours after surgery. The mean postoperative cardiac index was higher in the triiodothyronine group (2.97 +/- 0.72 vs. 2.67 +/- 0.61 liters per minute per square meter of body-surface area, P = 0.007), and systemic vascular resistance was lower (1073 +/- 314 vs. 1235 +/- 387 dyn.sec.cm-5, P = 0.003). The two groups did not differ significantly in the incidence of arrhythmia or the need for therapy with inotropic and vasodilator drugs during the 24 hours after surgery, or in perioperative mortality and morbidity. CONCLUSIONS: Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy.

Aged↗

PubMed1995

Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia.

Cardiopulmonary bypass results in a "euthyroid sick" state. Recently, interest has focused on the relationship between low serum triiodothyronine levels and postoperative cardiovascular hemodynamics. The present study was undertaken to more clearly define the acute effects of triiodothyronine on myocardial mechanics and energetics after hypothermic global ischemia using an ex-vivo canine heart preparation to model the clinical condition. Experiments were performed on isolated hearts subjected to hyperkalemic arrest with 90 minutes of hypothermic (10 degrees C) ischemia. Isolated hearts were cross-perfused by euthyroid support dogs in which triiodothyronine levels spontaneously decreased by 65% to 75% (p < 0.01) after the initiation of cross-perfusion. In nine heart preparations, triiodothyronine (Triostat) was given as a bolus dose (0.2 micrograms/kg) after 1 hour of baseline data collection with a subsequent measurable rise in serum triiodothyronine levels (p < 0.01). In six postischemic hearts, reverse triiodothyronine was given as a 0.2 micrograms/kg bolus. Triiodothyronine was also administered to a group of eight nonischemic, continuously perfused isolated hearts. Intrinsic myocardial contractility was assessed by analysis of the preload recruitable stroke work area, energetic efficiency from the myocardial oxygen consumption-pressure-volume area relationship, and coronary vascular resistance from analysis of coronary flow and perfusion pressure. Acute administration of triiodothyronine to postischemic hearts improved the preload recruitable stroke work area from 9.5 +/- 1.42 to 14.9 +/- 2.03 x 10(7) erg/ml, a 56% increase from baseline (p < 0.001), but had no effect on the preload recruitable stroke work area of the nonischemic hearts. The inotropic response resulting from triiodothyronine treatment did not alter the myocardial oxygen consumption-pressure-volume area relationship. Triiodothyronine treatment was associated with significantly decreased coronary resistance and increased coronary flow through a range of diastolic loading conditions in the postischemic hearts. The biologically inactive thyroid hormone metabolite reverse triiodothyronine was without effect on any of the measured parameters. On the basis of these results, we conclude that the low triiodothyronine state of cardiopulmonary bypass can be reproduced in this isolated heart model and that acute triiodothyronine treatment results in a unique inotropic action manifest only in the postischemic reperfused myocardium and is accomplished without oxygen wasting effects.

Animals↗

PubMed1994

Staged approach to combined repair of pectus excavatum and lesions of the heart.

The combined repair of severe pectus excavatum and cardiac lesions remains technically difficult. We report our experience with a patient undergoing such a combined repair of pectus and implantation of an aortic valved conduit in the setting of the Marfan syndrome. The procedure was staged such that the dissection and bony mobilization was done at the first procedure before heparin administration in combination with a sternal split and subsequent aortic repair. The second stage of sternal repositioning and cartilage resection was completed several days later with excellent cardiopulmonary and cosmetic results. The technique and a review of the literature are included.

Adult↗

PubMed1994

Combined aprotinin and erythropoietin use for blood conservation: results with Jehovah's Witnesses.

Despite recent advances in blood conservation techniques, major risks persist for excessive bleeding and blood transfusion after open heart operations. We reviewed the records of 100 consecutive patients undergoing first-time coronary artery bypass grafting at our institution to define these risks and develop a multimodality blood conservation program based on the results. This program was subsequently applied on a prospective basis to a select group of patients who refuse blood transfusion on religious grounds (Jehovah's Witnesses [JW]) (n = 15). Encouraging initial results with coronary artery bypass grafting in this group (n = 8) led to the application of the program to more complex operations (n = 7), including repeat bypass grafting with use of the internal mammary artery, repeat mitral valve replacement, aortic and mitral valve replacement with coronary artery bypass grafting, mitral valve replacement with bypass grafting, chronic type 1 dissection repair, aortic valve replacement, and atrial septal defect repair in 1 patient each. The blood conservation program employed in these patients included the use of (1) aprotinin (full Hammersmith regimen), (2) high-dose erythropoietin, (3) "maximal"-volume intraoperative autologous blood donation, (4) low-prime cardiopulmonary bypass, (5) exclusive use of intraoperative cell salvage, and (6) continuous reinfusion of shed mediastinal blood. There were no deaths in the JW group. Thromboembolic complications consisted of a transient posterior circulation stroke in only 1 patient (dissection repair). No blood or blood products were transfused compared with the transfusion of 5.1 +/- 7.8 units (mean +/- standard deviation) in the 100 primary coronary bypass patients in whom the blood conservation program was not employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗