Biomedical subjects

C F Zwemer

Publications and source records attributed to C F Zwemer.

7 recordsLinked to original sources

PubMed2000

Hyperoxic reperfusion exacerbates postischemic renal dysfunction.

BACKGROUND: Hyperoxic reperfusion from global ischemia worsens functional outcome because of oxygen radical-mediated injury. This study tested the hypothesis that hyperoxic reperfusion would exacerbate postischemic renal dysfunction. METHODS: Twenty-nine healthy, uninephrectomized, male mongrel rabbits (Oryctolagus cuniculus) in 3 groups were subjected to 30 minutes of complete normothermic renal ischemia followed by reperfusion under hyperoxic or normoxic conditions. The groups were: hyperoxically reperfused (n = 8), normoxically reperfused (n = 8), hyperoxic sham (no ischemia, n = 5), and allopurinol-pretreated (50 mg/kg, intravenously), hyperoxically reperfused animals (n = 8). Plasma concentrations of creatinine, urea nitrogen and electrolytes were measured at 0, 24, 48, and 72 hours after ischemia and served as functional outcome markers. Histopathologic analysis of kidneys for injury was performed by an expert who was blinded to the procedures. RESULTS: Plasma creatinine in hyperoxically reperfused rabbits was significantly elevated above normoxic (P =.02) and sham (P =.003) animals by 48 hours and remained elevated to 72 hours. Plasma urea nitrogen in hyperoxically reperfused rabbits was significantly elevated above the normoxic group (P = .01), the sham group (P = .02), and the allopurinol group (P = .04) by 72 hours. These coincided with a significantly elevated histopathologic injury score in hyperoxically reperfused rabbits compared with sham (P = .019), normoxic (P = .035), and allopurinol-pretreated hyperoxically reperfused animals (P = .037). CONCLUSIONS: Hyperoxic reperfusion exacerbates renal dysfunction after 30 minutes of complete normothermic ischemia. This dysfunction may be mediated by oxygen radical-related injury.

Allopurinol↗

PubMed1997

Acute thyroid hormone administration increases systemic oxygen delivery and consumption immediately following resuscitation from cardiac arrest without changes in thyroid-stimulating hormone.

This study determined the acute effects of intravenous levothyroxine sodium (LT4) on systemic oxygen delivery and consumption for 6 h following resuscitation from 9 min of normothermic cardiac arrest in dogs. Male mongrel dogs (15-25 kg) were randomly assigned to two groups of seven. The treated group received a pre-cardiac arrest infusion of 15 micrograms/kg per h of LT4 for 1.5 h prior to arrest and for 6 h after, while controls received a comparable volume of 0.9 N saline infusion. Neurologic outcome was recorded at 1, 2 and 6 h following resuscitation. Systemic oxygen consumption (VO2), carbon dioxide production (VCO2) and respiratory quotient (RQ) were calculated from directly measured cardiac output, arterial and mixed venous blood gases and contents. Serum levels of circulating canine thyroid-stimulating hormone (cTSH), total thyroxine (T4), free thyroxine (FT4), total 3,5,3'-triiodothyronine (T3), free 3,5,3'-triiodothyronine (FT3), reverse 3,3',5'-triiodothyronine (rT3), and plasma markers of oxidant injury (malonaldehyde (MDA), 4-hydroxynonenal (4-OH) and erythrocyte GSH) were measured before administration and after resuscitation. Following resuscitation, treated dogs maintained significantly higher cardiac output when compared with their control counterparts at 4 h (5.5 ml/g per h vs. 2.9 ml/g per h, respectively, P < 0.05) and at 6 h (5.5 ml/g per h vs. 3.0 mg/g per h, respectively, P < 0.05). The level of VO2 was significantly higher in treated dogs than control dogs at 1, 4 and 6 h (P < 0.05). Treated dogs had significantly elevated levels of T4, FT4, T3, FT3 and rT3 (P < 0.01), compared with control dogs. No changes in cTSH were detected between groups or over time. Acute administration of LT4 enhances systemic oxygen delivery and apparently, therefore, oxygen consumption following resuscitation.

Animals↗

PubMed1997

Gender differences in 24-hour outcome following resuscitation after 9 minutes of cardiac arrest in dogs.

OBJECTIVE: To examine possible gender-specific differences in 24-hr outcome following resuscitation from 9 mins of controlled cardiac arrest. DESIGN: Preclinical, prospective study comparing two similarly prepared, independent control groups (one female group, one male group) included in a larger series of studies. SETTING: Physiology research laboratory at a major medical center. SUBJECTS: Male and female mongrel dogs (Canis familiaris), weighing 16 to 22 kg. INTERVENTIONS: Cardiopulmonary-cerebral resuscitation following 9 mins of normothermic cardiac arrest in male vs. female dogs. MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure, heart rate, urine output, arterial blood oxygen, and PCO2 values, arterial pH, temperature, plasma glucose concentrations, and hematocrit were measured and recorded at the precardiac arrest and postcardiac arrest period, and at 30 mins, and 1, 4, 6, 12, and 24 hrs following resuscitation. Neurologic dysfunction was assessed using a well-standardized neurologic deficit score assigned at 6, 12, and 24 hrs after arrest. Plasma concentrations of malonaldehyde, 4-hydroxynonenal, and erythrocyte-reduced glutathione were measured at the precardiac arrest period, and 6, 12, and 24 hrs following resuscitation. Additionally, serum concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, gamma-glutamyl transferase, creatinine kinase, creatinine, albumin, and total protein were measured before arrest, and at 6, 12, and 24 hrs after resuscitation. Plasma concentrations of inorganic phosphorus, blood urea nitrogen, and electrolytes (sodium, chloride, calcium, and potassium) were measured. The estrous cycle phase in the female dogs enrolled in the study was determined by physical examination and vaginal cytology. No prearrest differences were detectable between males and females in basic physiologic variables. No differences in neurologic deficit were detectable between males and females across the 24-hr recovery period following resuscitation. No detectable differences in malonaldehyde, 4-hydroxynonenal, and erythrocyte-reduced glutathione occurred between groups. Serum concentrations of aspartate aminotransferase (p = .02), alanine aminotransferase (p = .009), creatinine kinase (p = .01), total bilirubin (p = .05), and plasma concentrations of inorganic phosphorus (p = .03), blood urea nitrogen (p = .0003), and creatinine (p = .02) all were significantly and dramatically higher in female than male dogs at the 24-hr time point. The trend of increase in these values began at the 6- and 12-hr time points and was consistent with a steadily decreasing trend in mean arterial pressure and an increasing trend in heart rate in the female group. CONCLUSIONS: An extensive history with this preclinical canine model (restricted to male dogs) had indicated little or no change in standard clinical chemistry markers of systemic dysfunction following 9 mins of cardiac arrest. However, when compared with male dogs, the female dogs tested here appear to have sustained a more significant hepatic and renal ischemic injury with no differences in the neurologic deficit.

Alanine Transaminase↗

PubMed1996

Systemic pressor response during hindlimb ischemia is inversely related to femoral artery pressure and fractional inspired oxygen.

BACKGROUND: Delayed-onset reflex increases in mean arterial pressure (MAP) occur during clamping of the infrarenal aorta. This study investigated the afferent limb of the reflex by independently altering femoral artery blood pressure (FBP) or fractional concentration of inspired oxygen (FIO2) while monitoring systemic arterial blood pressure. METHODS: The infrarenal aorta was divided, and an occlusive roller pump delivered incremental flow to the distal aorta thus controlling FBP. In six dogs the FBP was reduced in random order to 50, 40, 30, 20, and 10 mm Hg and held constant for 30 minutes. In another six dogs the FBP was held at 20 mm Hg, whereas the FIO2 was randomly varied among 0.13, 0.21, and 1.0 for 30-minute intervals. RESULTS: Under these conditions MAP was significantly and inversely correlated with FBP (MAP was 172 +/- 8 mm Hg when FBP was 10 mm Hg, p < 0.0001; MAP was 158 +/- 8 mm Hg when FBP was 20 mm Hg, p = 0.0001; MAP was 138 +/- 7 mm Hg when FBP was 30 mm Hg, p = 0.0048; and MAP was 130 +/- 7 mm Hg when FBP was 40 mm Hg, p = 0.0045). MAP was significantly and inversely related to the FIO2 value when FBP was fixed at 20 mm Hg (MAP of 186 +/- 9 mm Hg at FIO2 of 0.13 and was significantly higher than MAP of 163 +/- 11 mm Hg at FIO2 of 0.21, p = 0.01; and MAP of 157 +/- 10 mm Hg at FIO2 of 1.0, p = 0.0001). CONCLUSIONS: The magnitude of the delayed systemic pressor response is inversely proportional to the FBP. We suggest that this pressor response is also particularly sensitive, in part, to arterial blood oxygen tension when hindlimb perfusion pressure is low.

Animals↗

PubMed1996

Acute administration of T3 or rT3 failed to improve outcome following resuscitation from cardiac arrest in dogs.

Documentation of profound changes in serum thyroid hormone concentrations associated with cardiac arrest and resuscitation, as well as other acute emergencies, have spurred evaluation of possible therapeutic thyroid hormone administration. Acute and significant, this state, characterized by abnormally low serum thyroid hormone concentrations, may indicate selective thyroid replacement therapy. In a previous investigation, post-resuscitation infusion of levothyroxine sodium (L-T4) to normalize serum 3,5,3'-triiodothyronine (T3) concentrations was associated with significant reduction of neurologic deficit caused by severe global cerebral ischemia. Since L-T4 has been reported to act directly or via one of its metabolites, most likely T3, this most active form of thyroid hormone was tested. When L-T4 reduced the neurologic deficit, an increase in 3,3',5'-triiodothyronine (rT3) was also observed. This study therefore determined whether a post-resuscitation treatment with either T3 (n = 8) or rT3 (n = 8) provided protection against global cerebral ischemia comparable to that of L-T4. Global cerebral ischemia was achieved with 9 min of ventricular fibrillation. Following resuscitation, one of three solutions (saline group as a control) was infused for 24 h at rates that reproduced the normal serum T3 concentrations or the rT3 concentrations achieved previously during the L-T4 therapy. The successful elevation of T3 and mimicking rT3 concentrations was assessed and confirmed by radioimmunoassay (RIA). In addition, TSH levels were measured by a novel RIA specific for canine thyroid-stimulating hormone (cTSH). Neurologic deficit was assessed with a well-standardized neurologic deficit examination. In contrast to previous studies using L-T4 infusion, no significant reduction of neurologic deficit was observed. Serum thyroid hormone changes confirmed previously described decreases and in no case did changes in cTSH appear causal in these changes. Thus, we concluded that L-T4 may offer a therapeutic advantage over T3 or rT3.

Animals↗

PubMed1995

Hypoxic cardiopulmonary-cerebral resuscitation fails to improve neurological outcome following cardiac arrest in dogs.

Hyperoxic cardiopulmonary resuscitation (CPR) is associated with an increase in neurologic dysfunction upon successful resuscitation with much of the damage attributable to an increase in reperfusion oxidant injury. We hypothesized that by contrast, hypoxic ventilation during resuscitation would improve neurologic outcome by reducing available substrate necessary for oxidant injury. Specifically, this study investigated the effects of 2 levels of hypoxic ventilation during resuscitation: F1O2 = 0.085, PaO2 = 26.6 +/- 3.4 mmHg, (HY8), and F1O2 = 0.12, PaO2 = 33.0 +/- 4.2 mmHg, (HY12), and normoxic resuscitation: F1O2 = 0.21, PaO2 = 60.6 +/- 17.0 mmHg, (N) on survival and neurological outcome following 9 min of normothermic cardiac arrest. Concentrations of malonaldehyde (MDA) and 4-hydroxynonenal (4-OH) in plasma and concentrations of glutathione (GSH) in erythrocyte lysates were measured to quantify possible radical damage. Physiological variables including arterial blood gases were followed for 24 h after resuscitation. Neurologic outcome was assessed using a standardized scoring system. Hypoxically (HY8) resuscitated dogs tended to have a greater neurologic deficit than normoxically resuscitated dogs and had reduced overall survival (16.9 +/- 8.9 h) compared to N dogs (24.0 +/- 0.0 h). Overall survival time correlated negatively (-0.693) and significantly (P = 0.0018) with plasma glucose concentration. Arterial plasma glucose concentrations were higher in the HY8 group compared to the N group immediately (HY8, 312 +/- 86 mg/dL; N, 196 +/- 82 mg/dL; P = 0.17) and 30 min (HY8, 331 +/- 109 mg/dL; N, 187 +/- 74 mg/dL; P = 0.077) following resuscitation. No statistically discernible differences in markers of oxidant injury were apparent among the 3 groups, but pooled data increased significantly with time for MDA and 4-OH. Pooled data for GSH showed a significant drop at 1 h following resuscitation and returned to normal by 6 h. Data from these markers suggested attendant oxidant injury in all groups. Thus, hypoxic ventilation at 2 depths of hypoxia during resuscitation failed to improve neurologic outcome beyond that achieved by ventilation with air, suggesting that normoxia rather than hyperoxia or hypoxia is the ideal target for arterial oxygenation during resuscitation.

Aldehydes↗

PubMed1994

Cardiopulmonary-cerebral resuscitation with 100% oxygen exacerbates neurological dysfunction following nine minutes of normothermic cardiac arrest in dogs.

This study investigated the effects of normoxic (FIO2 = 0.21), hyperoxic (FIO2 = 1.0), and hyperoxic (FIO2 = 1.0) plus antioxidant pretreatment (tirilazad mesylate) [corrected] resuscitation on neurologic outcome following 9 min of normothermic (39 +/- 1.0 degrees C) cardiac arrest. Physiologic variables including arterial blood gases and neurologic outcome, which was assessed using a standardized scoring system, were followed over a 24-h period following resuscitation from cardiac arrest. Hyperoxically resuscitated dogs sustained significantly worse neurological deficit at 12 and 24 h (mean scores: 39 +/- 3 and 49 +/- 8, respectively) than did antioxidant pretreated hyperoxically resuscitated dogs (mean scores: 22 +/- 1, P = 0.0007 and 22 +/- 1, P = 0.004, respectively) and normoxically resuscitated dogs (mean scores: 28 +/- 4, P = 0.025 and 33 +/- 8, P = 0.041 respectively). These data suggest that oxidant injury has a major role in central nervous system dysfunction following successful resuscitation from 9 min of cardiac arrest. Also, resuscitation from cardiac arrest with hyperoxic FIO2's may contribute to and further exacerbate neurologic dysfunction.

Animals↗