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Biomedical subjects

C G McGregor

Publications and source records attributed to C G McGregor.

At least 19 recordsLinked to original sources
PubMed1992

Molecular cloning and characterization of the platelet-activating factor receptor gene expressed in the human heart.

PAF decreases cardiac contractility and blood pressure. To characterize the cardiac PAF receptor, we screened a human ventricular cDNA library in a low stringency condition, using a PCR product derived from guinea pig lung PAF receptor as a probe. Four clones were obtained and named HV1-4. In Xenopus oocytes injected with cRNA derived from HV3 or 4 but not from HV1 or 2, PAF elicited a Ca(2+)-activated Cl- current. HV3 and HV4 were duplicate clones, encoding a 342 amino-acid polypeptide which was identical to that of the human leukocyte PAF receptor. However, a portion of the 5' untranslated region of HV3 (or 4) was different from that of the leukocyte receptor cDNA. Northern blotting of human ventricles and atria using the HV3 insert showed a single band of approximately 4 kb. These results suggest a tissue-specific translational mechanism responsible for regulation of the expression of the PAF receptor mRNA in these tissues.

Amino Acid Sequence↗
PubMed1992

The development of cardiac transplantation.

The history of cardiac transplantation provides an excellent prototype for the development of a therapeutic technique. The first observations on cardiac transplantation were made in animal models in the early 20th century. Surgical problems were solved through a series of technologic advances, and problems associated with immune-mediated rejection were discovered and successfully addressed. By the late 1960s, cardiac transplantation in humans had become feasible. Since the first successful transplantation of a heart in a human in 1967, the management of rejection and infection has steadily progressed, and the long-term outcome after cardiac transplantation has improved dramatically. The success of cardiac transplantation has led to an expansion of the potential recipient pool to include children and adults in the eighth decade of life. Unfortunately, the growth of cardiac transplantation has resulted in an inadequate supply of suitable donor hearts. The limited supply of donor hearts has provided the impetus for further research in xenotopic cardiac transplantation and for the development of implantable circulatory assist devices.

Animals↗
PubMed1992

Cardiac transplantation: surgical considerations and early postoperative management.

The limited availability of donor hearts is the major constraint to the expanded application of cardiac transplantation. As many as 25% of potential recipients will die before a donor becomes available. Since 1986, hospitals that receive Medicare and Medicaid funds have been required to ask family members of all brain-dead patients who are potential donors whether they have considered organ donation. The United Network for Organ Sharing is responsible for the national organ procurement and transplantation network as well as the national organ transplantation scientific registry. The increasing occurrence of multiorgan donation is amplifying the demands for intensive-care management of donors. Donor and recipient are matched on the basis of ABO blood group and body size. The donor operation can be performed in any standard operating room. Although the maximal acceptable ischemic time for a donor heart is 4 to 6 hours, briefer preservation times result in better hemodynamic performance after transplantation and a significantly lower 30-day mortality. The technique of choice in most medical centers is orthotopic cardiac transplantation. Postoperatively, most patients remain in the intensive-care unit for 1 or 2 days and in the hospital for 1 to 2 weeks. Standard intensive-care procedures after transplantation, including nursing and cardiovascular management as well as the treatment of failure of the donor heart, are reviewed. A comprehensive educational program for patients and their families should optimize the outcome after heart transplantation. The overall charges for heart transplantation averaged $114,000 in 1987, 80% of which were hospital charges.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Protocols↗
PubMed1992

Total lymphoid irradiation: a novel and successful therapy for resistant cardiac allograft rejection.

Total lymphoid irradiation (TLI) is a novel type of adjuvant immunosuppression for patients who undergo cardiac transplantation and have refractory allograft rejection during standard immunosuppressive therapy. TLI consists of 6 to 10 fractions of 80 cGy (1 cGy = 1 rad) of irradiation to lymphatic tissues with use of the standard mantle and inverted Y fields. We have used TLI in six patients with biopsy-proven rejection that was refractory to standard treatments, including cyclosporine, azathioprine, antilymphocyte antibodies, and corticosteroids. In five patients, recalcitrant rejection was resolved after completion of TLI, and resolution persisted during long-term follow-up (17 to 30 months; mean, 22.2 months). In each patient, a substantial increase in the CD8 (suppressor T-lymphocyte) subset and elimination of B lymphocytes were demonstrated, findings that also persisted. Side effects were mild and primarily limited to transient leukopenia. In four patients, a readily treated cytomegalovirus reactivation was noted during TLI; thus, a causal relationship was suggested. In recipients of cardiac allografts who have refractory rejection, TLI provides long-lasting amelioration of the rejection profile. This result may be attributable to a relative enhancement of the suppressor T-cell subset and elimination of the B-lymphocyte line. Side effects are minimal, but monitoring for cytomegalovirus activation or reactivation is recommended.

Adult↗
PubMed1992

Pathology of surgically excised primary cardiac tumors.

Between 1957 and March 1991, 106 patients with 110 neoplasms that originated in the heart were treated surgically at the Mayo Clinic and had pathologic material available for review. The study group consisted of 39 male and 67 female patients, who ranged in age from 2 to 80 years. Benign atrial myxomas (64 in the left atrium and 16 in the right atrium) were the most commonly encountered neoplasm. The other benign tumors were nine fibromas, five lipomatous tumors, seven valvular fibroelastic papillomas, and one cardiac hamartoma (so-called oncocytic cardiomyopathy). In addition, eight patients had a primary cardiac malignant lesion: angiosarcoma, leiomyosarcoma, and malignant fibrous histiocytoma in two patients each and sarcoma (not otherwise specified) and osteogenic sarcoma in one patient each. The angiosarcomas originated in the right atrium, and the other malignant tumors originated in the left atrium. The histologic feature that most frequently predicted an adverse clinical outcome was the presence of mitotic figures, although highly cellular tumors and those with necrosis also tended to have a malignant course.

Adolescent↗
PubMed1992

Transient ultrastructural injury and repair of pulmonary capillaries in transplanted rat lung: effect of preservation and reperfusion.

A donor lung is injured during preservation and is generally thought to be further injured by reperfusion on transplantation. Donor lungs from 15 adult male Lewis rats preserved by flush perfusion with cold Marshall's solution at 4 degrees C were examined by scanning and by quantitative transmission electron microscopy after 2, 4, or 7 h of storage at 4 degrees C and after transplantation (syngeneic) at 4 or 12 h (six animals per time interval). During preservation of the donor lung, capillary morphology changed rapidly. Both endothelial cells and type I pneumonocytes thinned (surface/volume ratio increased by 2 h in both; P less than 0.001). Pericapillary edema developed involving the blood-gas barrier. Basement membrane thickness increased significantly (P less than 0.001). Occasional breakage of the endothelial cell sheet occurred after 4 h of preservation, but even after 7 h of preservation there was no evidence of irreversible cell damage. The lamellar bodies of type II pneumocytes aggregated. Changes increased in severity with increase in preservation time. After transplantation, type I and type II pneumonocytes recovered after 12 h, but it took longer for the endothelial cell morphology to recover. Edema decreased rapidly during the first 4 h, despite the number of adherent neutrophils increasing 3-fold. The pulmonary capillaries of the transplanted lung showed no structural evidence of additional reperfusion injury, indicating a satisfactory method of preservation.

Animals↗
PubMed1992

Pulmonary arterial reactivity after transplantation. Differential effects of denervation and rejection.

Little is known regarding changes in reactivity of the vasculature of transplanted solid organs. Experiments were designed to differentiate the effects of denervation and rejection on the function of the endothelium and smooth muscle of pulmonary arteries in transplanted lungs of the dog. Single lungs were transplanted as autografts to study the effects of denervation or as allografts to study the additional effects of rejection. Immunosuppression was stopped in animals receiving allografts 5 days after operation, and rejection was allowed to proceed for an average of 3 days. Animals receiving autografts were studied after the same time period. There were no differences in concentrations of circulating leukocytes, platelets, or lymphocytes between the two groups. Circulating concentrations of angiotensin-converting enzyme were significantly reduced during rejection; concentrations of endothelin were unchanged. Rings of pulmonary arteries with and without endothelium were suspended for the measurement of isometric force in organ chambers. Contractions to angiotensin I and endothelin were less in rejecting than in autotransplanted arteries, whereas those to 5-hydroxytryptamine were enhanced. Contractions to norepinephrine were comparable in both autograft and rejecting allograft arteries. Relaxations to isoproterenol were greater in the autograft than in the rejecting autografted arteries; the opposite was observed for relaxations to histamine. Endothelium-dependent relaxations to adenosine diphosphate and bradykinin but not to calcium ionophore A23187 were reduced with rejection; relaxations to nitric oxide were unchanged. These results suggest that transplantation per se affects vascular reactivity. However, there are selective dysfunctions of receptor-operated mechanisms in arteries that are associated with rejection and that are distinct from denervation. Further, serum concentrations of angiotensin-converting enzyme may be an indicator of rejection of transplanted lungs.

Animals↗
PubMed1991

Surgical factors affecting growth potential of the immature rat lung.

The transplanted immature rat lung has been shown capable of fulfilling its growth potential after left lung transplantation (LLTx) and concomitant right cardiac lobe resection (RCLR). However, unexpected findings in these studies included an abnormal rise in lung volume in the contralateral lung due to alveolar multiplication, and significant dilatation of the bronchi in the transplanted left lung. In the present study, the influence of surgical factors that could have contributed to these changes, i.e. RCLR, denervation, and anastomotic stenosis, were studied individually. Immature Lewis rats aged 4 and 6 weeks were used and (a) RCLR, (b) RCLR and right hilar stripping, and (c) RCLR and left pulmonary artery (PA) banding were performed in groups 1 (n = 12), 2 (n = 5) and 3 (n = 6), respectively. Animals were killed after 6 months and the lungs studied using quantitative morphometric techniques. In groups 1 and 2, right lungs did not show any significant increase in volume. Alveolar number and airway diameter in both lungs in all groups were not significantly different from controls. In group 3 both right and left lungs presented an increase in alveolar size (p less than 0.02 on the right and p less than 0.01 on the left). Changes seen after LLTx in the rat, such as alveolar multiplication, cannot be explained by compensatory growth (RCLR), denervation (RCLR and hilar stripping), or arterial stenosis at the anastomotic site (RCLR and left PA banding), but must be regarded as a consequence of transplantation per se. A role for neuropeptides in lung growth following transplantation is suggested.

Animals↗
PubMed1991

Hypertonic citrate solution as an alternative to modified Euro-Collins' solution for lung preservation.

In a canine model of acute ischemic lung injury, a hypertonic citrate solution (HTC) widely used for renal preservation in the United Kingdom, was compared with modified Euro-Collins' solution (ECS) currently the most widely clinically used pulmonary perfusate. Ten beagle dogs underwent left thoracotomy and exclusion of the left lung in situ. The lung was flushed with 30 ml/kg of either HTC or ECS and subjected to 60 min of warm ischemia. The circulation to the lung was then restored, the contralateral lung excluded, and the animal ventilated at a fixed FiO2 of 0.4 for 4 hr. Lung function was assessed by arterial oxygenation and hemodynamic measurements and, following sacrifice, by lung weight gain, bronchoalveolar lavage, and ultrastructural studies. Flush perfusion with HTC was associated with significantly less severe reperfusion injury, as determined by superior arterial oxygenation (PaO2 at 1 hr: HTC--152 mmHg [(95% confidence interval) CI] [122-182], ECS--59 [47-70]; PaO2 at 4 hr: HTC--124 [100-149], ECS--51 [42-61]), lower pulmonary vascular resistance index (PVRI at 4 hrs: HTC--838 dynes sec cm-5m-2 [651-1075], ECS--1233 [963-1588]); and lower lung weight (HTC--85 g [66-107], ECS--146 [114-184]). Bronchoalveolar lavage studies demonstrated an influx of neutrophils following reperfusion that was significantly less marked in the HTC group (increase in % neutrophils: HTC 24 [19-29], ECS 77 [72-82]). Lung injury assessed by electron microscopy tended to be less severe in the HTC animals. We conclude that HTC may offer an alternative superior to ECS for lung preservation.

Animals↗
PubMed1991

Methods of cardiac preservation alter the function of the endothelium in porcine coronary arteries.

This study was undertaken to determine whether clinical methods for preservation and storage of hearts explanted for transplantation affect the responsiveness of coronary arteries to vasoactive agents. Porcine hearts were perfused with crystalloid or blood cardioplegic solution. Rings of coronary arteries were suspended in organ chambers for measurement of isometric force (1) immediately after perfusion and (2) after 5 hours' storage of the hearts at 4 degrees C in the same cardioplegic solution (n = 6 in each group). The maximal contraction of the smooth muscle to potassium chloride, 40 mmol/L, was reduced significantly after perfusion with crystalloid cardioplegic solution (10.8 +/- 1.2 gm) compared with blood cardioplegic solution (17.3 +/- 0.8 gm) and nonperfused coronary arteries (control group 16.9 +/- 1.8 gm). The sensitivity of the arteries with endothelium to the contractile effects of prostaglandin F2 alpha increased after perfusion with crystalloid cardioplegic solution (ED50, [-log mol/L] 5.8 +/- 0.04) compared with blood cardioplegic solution (5.3 +/- 0.02) and the control group (5.7 +/- 0.03). In addition, relaxations to the calcium ionophore A23187, bradykinin, and the alpha 2-agonist BHT-920, which depend on the presence of endothelial cells, were significantly reduced after perfusion with crystalloid compared with blood cardioplegic solution or the control group. The responsiveness of the endothelium and smooth muscle after 5 hours' cold storage was unaltered in the blood cardioplegia group, whereas storage resulted in functional recovery in the crystalloid cardioplegia group, with the result that all groups were comparable. These data suggest an immediate and reversible change in vascular function with crystalloid cardioplegia, which was not apparent with blood cardioplegia.

Animals↗
PubMed1990

Transesophageal echocardiography in critically ill patients.

The feasibility, safety and clinical impact of transesophageal echocardiography were evaluated in 51 critically ill intensive care unit patients (28 men and 23 women; mean age 63 years) in whom transthoracic echocardiography was inadequate. At the time of transesophageal echocardiography, 30 patients (59%) were being mechanically ventilated. Transesophageal echocardiography was performed without significant complications in 49 patients (96%), and 2 patients with heart failure had worsening of hemodynamic and respiratory difficulties after insertion of the transesophageal probe. The most frequent indication, in 25 patients (49%), was unexplained hemodynamic instability. Other indications included evaluation of mitral regurgitation severity, prosthetic valvular dysfunction, endocarditis, aortic dissection and potential donor heart. In 30 patients (59%), transesophageal echocardiography identified cardiovascular problems that could not be clearly diagnosed by transthoracic echocardiography. In the remaining patients, transesophageal echocardiography permitted confident exclusion of suspected abnormalities because of its superior imaging qualities. Cardiac surgery was prompted by transesophageal echocardiographic findings in 12 patients (24%) and these findings were confirmed at operation in all. Therefore, transesophageal echocardiography can be safely performed and has a definite role in the diagnosis and expeditious management of critically ill cardiovascular patients.

Echocardiography↗
PubMed1990

Systolic coronary occlusion due to myocardial bridging--a rare cause of ischaemia.

Myocardial bridging causing systolic occlusion of the left anterior descending coronary artery was identified in a 47-year-old man with angina. A fixed anterolateral wall defect was demonstrated on thallium imaging and he underwent successful division of the bridge resulting in abolition of his symptoms and disappearance of the thallium defect.

Cardiomyopathies↗
PubMed1990

The use of a prostacyclin analog, iloprost, as an adjunct to pulmonary preservation with Euro-Collins solution.

The addition of prostaglandin to the single-flush technique of lung preservation is considered to enhance subsequent graft function. We have evaluated the use of the prostacyclin analog, Iloprost, in an animal model of unilateral lung transplantation. Group 1 (n = 5) received Iloprost as a pretreatment intravenously (20 ng/kg/min) and as an additive (20 ng/L) to 20 ml/kg of modified Euro-Collins solution. Group 2 (n = 5) received no Iloprost, either as pretreatment or added to the perfusate. Perfusate distribution within the lungs during flush perfusion was assessed using 99mTc-labelled microaggregates of albumin. After the initial preservation technique the lungs in both groups were stored for 6 hr in Euro-Collins solution at 4 degrees C. Thereafter, left lung transplantation was followed by ligation of the contralateral pulmonary artery and bronchus, rendering the animal completely dependent on the transplanted, stored lung. Preservation was assessed by animal survival, measurement of hemodynamic and blood gas data for 24 hr at a fixed FiO2 (0.4) and tidal volume (10 ml/kg), and at sacrifice by measurement of transplanted lung water. By these criteria, both group 1 and 2 lungs were well preserved. The addition of Iloprost to group 1 animals appeared to confer no measureable benefit in terms of lung cooling, perfusate distribution, postoperative graft function, or total lung water.

Animals↗
PubMed1990

Growth potential of the immature transplanted lung. An experimental study.

Syngeneic (Lewis to Lewis) and allogeneic (Brown Norway to Lewis) unilateral left lung transplants were performed on immature rats at 6 weeks of age at a time when alveoli are still multiplying after birth. Left lung denervation without transplantation was performed in a further group of rats (Lewis) by stripping the hilum, at 4 and 6 weeks of age. Animals were killed at either 2 weeks or 6 months after operation. Right and left lungs were analyzed separately by light microscopic quantitative techniques and findings were compared with findings from control animals matched for age and strain. The transplanted left lung in both syngeneic and allogeneic animals continued to grow to a normal size by formation of new alveoli, despite the presence of low-grade rejection activity in the immunosuppressed allogeneic group. The airways showed an increase in diameter for age at the hilum and periphery (p less than 0.01 and less than 0.001, respectively). The volume of the contralateral right lung was greater than normal because of an increase in number (p less than 0.01) and size of alveoli for age. Denervation alone was associated with normal growth of both lungs. Thus it appears that, in rats, the transplanted immature lung can fulfill its growth potential.

Animals↗
PubMed1990

Evolution of heart transplantation.

Heart transplantation has evolved from preliminary animal experimentation in the early part of this century to an accepted orthodox therapy for many patients with end-stage cardiac disease in the 1980s. The development of successful heart transplantation is traced from the laboratory to early clinical attempts and the subsequent validation of this therapy, principally by the Stanford group in the 1970s. The dramatic worldwide impact of the use of cyclosporine for immunosuppression in the practice of heart transplantation is reviewed. Resultant changes in the practice of heart transplantation are discussed as well as the future developments of totally implantable circulatory support systems and xenografting.

Age Factors↗