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Biomedical subjects

C Haisch

Publications and source records attributed to C Haisch.

35 records · Page 2Linked to original sources
PubMed1994

Organ preservation without extreme hypothermia using an Oxygen supplemented perfusate.

All methods of organ preservation depend upon hypothermia to depress metabolism during storage. Yet, hypothermia may represent the rate-limiting factor in organ preservation. A new perfusate has been developed which supports organ preservation without extreme hypothermia. The perfusate consists of a complex fluid supplemented with an oxygen carrying perfluorocarbon emulsion, Oxygent (Alliance Pharmaceutical Corp,). The perfusate was used to preserve canine kidney autografts using pulsatile preservation at 32 degrees C and static storage at 25 degrees C. Upon autografting the dogs produced urine within minutes of reperfusion. These results indicate the new perfusate may have significant potential in organ preservation without extreme hypothermia.

Animals↗
PubMed1994

Postmortem organ salvage using an Oxygen supplemented perfusate.

The world-wide shortage of organs for clinical transplantation is caused by the limited existing donor pool of heartbeating cadavers. Attempts to expand into the nonheartbeating cadaver population have been hindered by warm ischemic damage. We evaluated if a new Oxygent (Alliance Pharmaceutical Corp.) supplemented perfusate could be used to salvage canine kidneys postmortem. The kidneys preserved in the Oxygent perfusate could be maintained in situ for time points ranging from one-eight hours postmortem; enough time to declare death and obtain consent for organ donation. In contrast, the control kidneys yielded abnormal histologic findings and impaired flow dynamics. These results suggest that new perfusate may have significant potential to expand the existing organ donor pool.

Adenosine↗
PubMed1993

Reduction in primary nonfunction of pancreas islet transplants with antithymocyte globulin agents, deoxyspergualin, and splenectomy.

These results suggest that DSG and RATG are an especially favored combination in reducing PNF of discordant pig islet xenografts, probably related to the effect of DSG on the macrophage, humoral antibody, or blockade of NK cell activity. More effective immunosuppression such as demonstrated in this study could well be critical in permitting the application on discordant islet xenografts to human clinical diabetes.

Animals↗
PubMed1990

Functional diversity in vascular endothelial cells: role in coxsackievirus tropism.

Six plaque-purified virus isolates were obtained from liver and heart tissues of a DBA/2 mouse infected 7 days earlier with 10(4) PFU of coxsackievirus group B type 3. Each virus isolate was assayed in vitro for infectivity to vascular endothelial cells (VEC) of the liver, lungs, and heart. Both the percentage of VEC infected and the mean progeny PFU produced per infected VEC were determined. Virus isolates from the heart showed greater infectivity and replication in heart VEC than in VEC derived from either the liver or lungs. Similarly, virus isolated from the liver preferentially infected liver VEC. Virus receptor expression varied between VEC populations, as demonstrated by binding studies with a [35S]methionine-radiolabeled heart virus and by enzyme-linked immunoadsorption assay studies with a monoclonal antibody to the coxsackievirus group B type 3 receptor on heart tissue. Finally, the heart and liver virus isolates were injected (10(4) PFU) intraperitoneally into BALB/c mice. After 7 days, the animals were sacrificed, and the hearts, livers, and lungs were evaluated for tissue injury and virus concentrations. Viruses originally isolated from the heart preferentially infected the heart when reinjected into animals and caused severe myocarditis. Viruses originally derived from the liver most consistently reinfected the liver, although significant virus concentrations were also detected in the heart. The liver virus isolates, however, were incapable of causing myocarditis. Thus, selective tropism of viruses for particular organs in vivo corresponds to the ability of these isolates to infect VEC in vitro.

Animals↗
PubMed1989

Noninvasive cardiac risk stratification of diabetic and nondiabetic uremic renal allograft candidates using dipyridamole-thallium-201 imaging and radionuclide ventriculography.

The ability of noninvasive risk stratification using dipyridamole-thallium-201 (Tl-201) imaging and radionuclide ventriculography to predict perioperative and long-term cardiac events (myocardial infarction or cardiac death) was evaluated in 36 uremic diabetic and 29 nondiabetic candidates for renal allograft surgery. Of the 35 patients who underwent renal allograft surgery 8 +/- 7 months after the study, none had transient Tl-201 defects (although 13 had depressed left ventricular ejection fraction) and none developed perioperative cardiac events. During a mean follow-up of 23 +/- 11 months, 6 (9%) patients developed cardiac events. Logistic regression analysis was used to compare the predictive value of clinical data (including age, sex, diabetes, chest pain history, allograft recipient) and radionuclide data. Presence of transient Tl-201 defect and left ventricular ejection fraction were the only significant predictors of future cardiac events (p less than 0.01). No other patient variables, including diabetes or receiving a renal allograft, had either univariate or multivariate predictive value. All 3 patients with transient Tl-201 defects had cardiac events compared with only 3 of 62 (5%) patients without transient Tl-201 defect (p less than 0.0001). Mean left ventricular ejection fraction was lower in patients with cardiac events (44 +/- 13%) compared with patients without cardiac events (57 +/- 9%, p less than 0.005). Overall, 5 of 6 patients with cardiac events had either transient Tl-201 defects or depressed left ventricular ejection fraction. Dipyridamole-Tl-201 imaging and radionuclide ventriculography may be helpful in identifying uremic candidates for renal allograft surgery who are at low risk for perioperative and long-term cardiac events.

Adult↗
PubMed1989

Clinical and experimental aspects of viral myocarditis.

Picornaviruses are frequently implicated as the etiological agents of acute myocarditis. This association is based historically on serological evidence of rising antibody titers to specific pathogens and more recently on identification of viral genomic material in endocardial biopsy specimens through in situ hybridization. Only rarely is infectious virus isolated from either the patient or the heart during periods of maximum myocardial inflammation and injury. Thus, despite a probable viral etiology, much interest centers on the role of the immune system in cardiac damage and the likelihood that the infection triggers an autoimmune response to heart-specific antigens. Heart-reactive antibodies and T cells are found in most myocarditis patients, and immunosuppressive therapy has proven beneficial in many, though not all, cases. Furthermore, murine models of coxsackievirus group B type 3-induced myocarditis also demonstrate that virus infection initiates autoimmunity and that these autoimmune effectors are predominately responsible for tissue injury. How virus-host interactions overcome presumed self-tolerance to heart antigens is discussed, and evidence supporting various theories of virus-initiated autoimmunity and disease pathogenesis are delineated.

Animals↗
PubMed1982

Differential effects of intravenous anaesthetic agents on cell-mediated immunity in the Rhesus monkey.

Considerable evidence has accumulated to implicate general anaesthetic agents as a cause of post-surgical immune depression. In the present study we evaluated the immuno-suppressive effects of three in vivo administered anaesthetic agents on cellular immune function in sub-human primates which did not undergo surgery. Normal rhesus monkeys received a minimal anesthetic dose of ketamine HCl, meperidine HCl, or sodium pentobarbital. Peripheral blood mononuclear cells were assayed for mitogen-induced lymphocyte proliferative responses and cell-mediated cytotoxicity (CC), including antibody-dependent CC, spontaneous CC and alloimmune CC. In vivo administration of the three agents caused significant reduction in lymphocyte functional capabilities. Within 30 min after administration of ketamine HCl or sodium pentobarbital, cytotoxic effector function was significantly depressed, with variable recovery occurring at 48 hr; cytolytic effector function was not impaired after meperidine HCl or in untreated controls. Ketamine HCl selectively suppressed effector function; mitogen-induced lymphocyte proliferative responses were not suppressed. Monkeys given meperidine HCl showed stable effector function and depressed lymphocyte proliferative function. Effects from sodium pentobarbital were non-selective, with reduced cytotoxic and proliferative lymphocyte functions. In summary, this study shows that intravenous anaesthetic agents are immunosuppressive in primates and exhibit disparate effects on afferent and efferent expressions of cellular immunity.

Anesthetics↗
PubMed1979

Hemostasis in massively transfused trauma patients.

Twenty-seven patients requiring massive transfusions were studied prospectively to determine whether administration of stored, modified whole blood induced a primary disorder of hemostasis evidenced by generalized microvascular oozing. Platelet counts fell in proportion to the number of units of blood transfused. In contrast, the levels of factors V and VIII correlated poorly with the units of blood transfused, 85% of the total variation in the levels being due to influences other than transfused blood. Levels of all other clotting factors were unrelated to the number of units of blood given. Eight patients developed abnormal bleeding. The cause appeared to be dilutional thrombocytopenia in five patients, and DIC in three. In six of the eight, bleeding was controlled with platelet concentrates alone. Two patients were given cryoprecipitate also. The most useful laboratory test for predicting abnormal bleeding was the platelet count. Fibrinogen levels should be followed as an aid in the diagnosis of DIC. The BT, PT, and PTT were not helpful in assessing the cause of bleeding, unless they were greater than 1.5 times the control value. We recommend that any patient receiving massive transfusions who develops diffuse microvascular bleeding be given platelet concentrates. Platelet counts as high as 100,000 may be required to control bleeding from surgical wounds. It is not necessary to supplement transfusions of stored, modified whole blood with fresh blood or fresh frozen plasma.

Adolescent↗
PubMedDate not supplied

Ex vivo evaluation of organ function after cold ischemia.

An ex vivo perfusion of kidneys was performed at 34 degrees C after cold ischemia of 24, 48, 72, and 96 hours to evaluate organ function prospectively. The prospective evaluation of organ function followed static hypothermic storage of the kidneys in a solution representative of clinical organ preservation. The warm perfusion was performed with an acellular solution that supports oxidative metabolism of sufficient magnitude to restore urine flow ex vivo. The parameters of organ function evaluated included oxygen consumption, vascular resistance, urine flow, and glomerular filtration rates, which were correlated with the histologic findings. The results of this study suggest that kidneys exposed to 24 and 48 hours of cold ischemia demonstrated oxygen consumption rates and vascular dynamics similar to control kidneys without exposure to cold ischemia, indicating cell viability. When the cold ischemic period was increased beyond 48 hours of preservation, substantially reduced rates of oxygen consumption and increased vascular resistances were observed, representing a loss of viability confirmed histologically. However, organ function was found to be impaired after exposure to cold ischemia at every time point. These results suggest that cold ischemic exposure had a negative impact on immediate renal function once oxidative metabolism was restored, which was exacerbated as the cold ischemic period was extended. Furthermore, these findings suggest that although the renal cells were viable after cold ischemic exposure, the viability status did not result in immediate function. Therefore, assessment of an organ based solely on cell viability may falsely indicate a functional organ. It will be necessary to identify parameters of organ function that can distinguish reversibility from non-reversibility of cellular impairment to distinguish permanent functional disturbances. The ability to predict organ function prospectively will be an important aspect of any effective future expansion of the organ donor pool.

Animals↗
PubMedDate not supplied

Ex vivo resuscitation of kidneys after postmortem warm ischemia.

An ex vivo resuscitation of kidney function following substantial post mortem warm ischemia was attempted with the ultimate goal of overcoming the ischemic barriers in organ retrieval for transplantation. The resuscitation technology involved reperfusion at 32 degrees C with an acellular solution to reinstitute oxidative metabolism of sufficient magnitude to restore function after a substantial postmortem warm ischemic insult. The ability to resuscitate renal function at various time periods postmortem was evaluated. Resuscitation parameters included perfusion pressures, vascular flow rates, vascular resistances, restoration of diuresis with concordant urinary creatinine concentrations, and blinded histologic evaluations. The results of this study suggest that it may one day be feasible to resuscitate organs following as much as 2 hr of postmortem warm ischemia for clinical transplantation. An expanded donor pool consisting of allografts resuscitated post mortem from what is now considered to be the "non retrieval donor" could help alleviate the chronic organ shortage. Furthermore, since organs resuscitated ex vivo at 32 degrees C exhibited ongoing metabolism, which was artificially supported rather than inhibited by traditional hypothermia, diuresis was restored. The ability to collect and analyze urine during organ resuscitation and preservation may present the opportunity to assess organ function prospectively.

Animals↗