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Biomedical subjects

C R Valeri

Publications and source records attributed to C R Valeri.

At least 163 records · Page 9Linked to original sources

Reperfusion of ischemic lower limbs increases pulmonary microvascular permeability.

Lower torso ischemia and reperfusion has been shown to stimulate the generation of thromboxane (Tx)A2, leading to transient pulmonary hypertension and later to polymorphonuclear leukocyte accumulations in the lungs. This study investigated whether hind limb ischemia leads to increased pulmonary microvascular permeability. Anesthetized sheep (n = 6) previously prepared with a lung lymph fistula underwent 2 hr of tourniquet ischemia of both lower limbs. One minute following tourniquet release mean pulmonary arterial pressure (MPAP) rose from 14 +/- 1 to 36 +/- 4 mm Hg (p less than 0.05) and returned to baseline within 30 min. The pulmonary arterial wedge pressure of 4 +/- 1 mm Hg was unchanged. Plasma TxB2 levels rose from 211 +/- 21 to 304 +/- 52 pg/ml (p less than 0.05) 10 min after tourniquet release and were back to baseline at 30 min. Lymph flow (QL) rose from 4.3 +/- 0.6 ml/30 min to 8.3 +/- 1.8 ml/30 min (p less than 0.05); the lymph/plasma (L/P) protein ratio rose slightly but not significantly. In three sheep, inflation of a left atrial balloon increased left atrial pressure from 3 to 16 mm Hg. MPAP rose from 14 to 24 mm Hg. There was an increase in QL from 3.6 to 17 ml/30 min; the L/P protein ratio declined from 0.63 to 0.41. These results indicate that reperfusion following 2 hr of bilateral hind limb ischemia results in increased pulmonary microvascular permeability.

Animals↗

Regional hypothermia protects against ischemia-reperfusion injury in isolated canine gracilis muscle.

Regional hypothermia is known to protect many tissues from ischemic injury. We investigated the relationship between regional hypothermia and skeletal muscle ischemia-reperfusion injury in a bilateral in vivo isolated canine gracilis muscle model. In five anesthetized dogs, one gracilis muscle was subjected to 6 hours of ischemia followed by 1 hour of reperfusion while the contralateral muscle served as a nonischemic control. Localization and quantitation of skeletal muscle injury was determined by histochemical staining with triphenyl tetrazolium chloride (TTC) followed by computerized planimetry of the infarct size. Muscle pH and temperature were monitored continuously in the proximal, middle, and distal segments by using pH electrodes and needle thermistors. Muscle pH was calculated by use of the Nernst equation with temperature correction, and hydrogen ion washout rates (H+) were derived from the observed change in muscle pH during reperfusion. A significant (p less than 0.05) regional hypothermia was observed in the distal third of the muscle. The preischemic temperature in the distal muscle was 27 +/- 2 degrees (SEM) C, compared to 34 +/- 1 degree and 32 +/- 2 degrees C in the proximal and middle segments of muscle, respectively. This temperature gradient was sustained throughout the experiment. The distal third of the ischemic muscle demonstrated significantly less (p less than 0.05) injury than the proximal and middle thirds as measured by TTC infarct size (31 +/- 10%, compared to 71 +/- 3% and 78 +/- 6%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Progressive loss of fibronectin-mediated opsonic activity in plasma cryoprecipitate with storage. Role of fibronectin fragmentation.

Septic injured patients often manifest a deficiency of plasma fibronectin. Several studies have shown improvements in organ function in such patients following infusion of fibronectin-rich plasma cryoprecipitate, while other studies found no improvement. One explanation for these differences may be the use of plasma cryoprecipitate which has been stored for various time intervals prior to its use as a source of fibronectin. This investigation tested the hypothesis that the opsonic activity of fibronectin in cryoprecipitate may decline with increased storage duration. Using a bioassay of opsonic activity, we evaluated human plasma cryoprecipitate that was stored at either -20 or -80 degrees C for various intervals (2 weeks to 12 months) after its preparation from fresh donor plasma. Our findings demonstrated that the opsonic activity of fibronectin in cryoprecipitate declined with increasing time of storage. Significant loss (p less than 0.05) of opsonic activity was first evident after 2 months of storage. Storage at -80 degrees C did not prevent this decline in opsonic activity as compared to storage at -20 degrees C. Immunoblot analysis revealed extensive fragmentation of the dimeric fibronectin (440 kdaltons) and the presence of lower molecular weight fragments in 4- to 12-month-old plasma cryoprecipitate. Therefore, plasma cryoprecipitate of varying ages (storage time) when used as a source of fibronectin for replacement therapy to support phagocytic function in septic injured patients may result in different fibronectin-mediated responses. The decline in activity may be due, in part, to fragmentation of the fibronectin molecule.

Biological Assay↗

The 24-hour posttransfusion survival and lifespan of autologous baboon red cells treated with inositol hexaphosphate-polyethylene glycol or inositol hexaphosphate-adenosine triphosphate-polyethylene glycol to decrease oxygen affinity.

Baboon red cells were treated to reduce oxygen affinity by an osmotic-pulse procedure using dimethyl-sulfoxide. Inositol hexaphosphate (IHP) alone or IHP and adenosine triphosphate (ATP) were incorporated into the red cells in the presence of polyethylene glycol (PEG). The procedure produced variable increases in the red cell P50 value, i.e., the partial pressure of oxygen at which 50% of the hemoglobin was saturated. The effect of treatment of autologous baboon red cells on the 24-hour posttransfusion survival value and lifespan T50 value was measured using a double-label procedure. The data demonstrate that the increase in the P50 value of treated red cells was negatively correlated with the 24-hour posttransfusion survival value; the higher the P50 value, the poorer the 24-hour posttransfusion survival value. The 24-hour posttransfusion survival value for nontreated baboon red cells was 90% and the T50 value was 14 days. The IHP-ATP-PEG-treated red cells had significantly higher red cell ATP levels than did IHP-PEG-treated red cells. The 24-hour posttransfusion survival value was 68% for the IHP-ATP-PEG treated red cells and 52% for the IHP-PEG-treated red cells when the increase in P50 ranged from 10 to 20 mm Hg; the lifespan T50 value for both the IHP-ATP-PEG-treated red cells and the IHP-PEG-treated red cells was 15 days. Osmotic pulse treatment produced significant red cell injury manifested by the 24-hour posttransfusion survival value. However, modification of the RBC with IHP-PEG or IHP-ATP-PEG to decrease hemoglobin affinity for oxygen did not affect their lifespan.

Adenosine Triphosphate↗

Polycythemia and hydration: effects on thermoregulation and blood volume during exercise-heat stress.

We studied the effects of autologous erythrocyte infusion on thermoregulation and blood volume during exercise in the heat. Specifically, we wanted to determine whether heat-acclimated subjects, as well as hypohydrated subjects, would have a thermoregulatory advantage from acute polycythemia during exercise in the heat. Five heat-acclimated males attempted four heat stress tests (HSTs): two pre- and two postinfusion. Autologous erythrocyte infusion was accomplished with 500 ml of a NaCl-glucose-phosphate solution containing approximately 60% hematocrit. One HST, both pre- and postinfusion, was done while subjects were euhydrated, and one HST was done while subjects were hypohydrated (-5% of body wt). After 30 min of rest in a 20 degrees C antechamber, the HST consisted of a 120-min exposure (2 repeats of 15 min rest and 45 min walking) in a hot (35 degrees C, 45% relative humidity) environment. The findings concerning acute polycythemia in heat-acclimated subjects are summarized: 1) polycythemia increased (P less than 0.05) sweating rate and reduced (P less than 0.01) core temperature during exercise-heat stress for both euhydrated and hypohydrated subjects; 2) the erythrocyte infusion caused an increased (P less than 0.05) plasma volume and increased (P less than 0.01) blood volume; 3) the increased plasma volume was associated with an increased (P less than 0.05) total circulating protein mass; 4) the increased total circulating protein mass tended to better maintain plasma volume when hypohydrated; and 5) heat acclimation may increase extravascular protein mass. Therefore, it is concluded that erythrocyte infusion provides a thermoregulatory advantage during exercise in the heat for heat acclimated subjects when both euhydrated and hypohydrated.

Acclimatization↗

Selective lung leukosequestration after complement activation.

This study tests whether activated complement leads to a selective entrapment of polymorphonuclear leukocytes (PMN's) in the lungs. Awake sheep were infused for 5 min with zymosan-activated plasma (ZAP, 2.5 mg/ml) at a rate of 5 ml/min into the superior vena cava (IV, n = 4) or intra-arterially into the aortic arch or femoral artery (IA, n = 8). At the end of IV infusion, leukocyte counts fell from 8,862 to 1,631/mm3 (P less than 0.01). PMN counts across the lungs decreased by 74%. There were increases in plasma thromboxane (Tx) B2 from 114 to 2,733 pg/ml (P less than 0.01), mean pulmonary arterial pressure from 12 to 42 mmHg (P less than 0.01), and physiological shunt from 13 to 25% (P less than 0.05). Within 1 h lymph TxB2 levels had risen from 301 to 4,916 pg/ml (P less than 0.01), lung lymph flow (QL) rose from 3.7 to 11.1 ml/30 min (P less than 0.05), lymph-to-plasma protein ratio (L/P) remained unchanged at 0.63, and lymph protein clearance increased from 2.3 to 7.5 ml/30 min (P less than 0.05). Leukosequestration, quantitated by capillary PMN counting and by assaying the granulocyte marker myeloperoxidase, occurred relative to sham animals (P less than 0.05) in the lung and spleen but not in other organs. Intra-arterial ZAP infusion led to changes that were similar in magnitude and timing to the IV group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Electrical alternans and cardiac electrical instability.

We investigated the relationship between electrical alternans and cardiac electrical stability in a series of 20 dog experiments and in a pilot clinical study. Electrical alternans was detected in both the QRS complex and the ST-T wave by use of a novel multidimensional spectral technique. The magnitude of the alteration was expressed as the alternating electrocardiographic morphology index (AEMI), expressed as parts per million of waveform energy. Electrical stability in the dog preparations was assessed via the ventricular fibrillation threshold measurement, and in the clinical studies via programmed stimulation. In 10 dog experiments, systemic hypothermia resulted in a 60% decrease in ventricular fibrillation threshold (VFT) (p less than .0001) and a significant increase in both AEMI(QRS) form 3.7 +/- 3.0 to 1448 +/- 548 (p less than .0001) and AEMI(ST-T) from 43.9 +/- 18.4 to 19,178 +/- 5579 (p less than .0001). In 10 dog experiments, transient coronary artery ligation also resulted in a 60% decrease in VFT (p less than .0001), an increase from 76.3 +/- 46.5 to 245 +/- 11 in AEMI(QRS) (p less than .05), and an increase from 842 +/- 505 to 1365 +/- 392 in AEMI(ST-T) (p less than .002). In 119 observations in 20 animal experiments, the rank correlation between VFT and AEMI(QRS) was -.30 (p less than .001), with that between VFT and AEMI(ST-T) being -.55 (p less than .0001). In a double-blind pilot clinical trial consisting of 23 studies in 19 patients, the result of electrophysiologic testing was used as an independent measure of cardiac electrical stability. Alternation in waveform morphology identified the inducible patient population with a sensitivity of 92%, a positive predictivity of 70%, and a specificity of 50% (p less than .05). We conclude that analysis of subtle beat-to-beat variability in electrocardiographic morphology may provide a noninvasive measure of cardiac electrical stability.

Adult↗

Effects of stroma-free hemoglobin solutions on isolated perfused rabbit hearts and isolated perfused rat kidneys.

"Stroma-free" hemoglobin solutions (SFH) cause hemodynamic alterations indicative of vasoconstriction. We studied vasoconstrictor activity in isolated rabbit hearts and rat kidneys of unmodified SFH and of SFH modified by pyridoxylation or glyoxylation, with or without glutaraldehyde cross-linking. The purity and chemical composition of the solutions, all prepared by other laboratories, were not characterized by us. In isolated hearts SFH prepared by conventional methods had potent vasoconstrictor activity. Pyridoxylation or purification by ion exchange chromatography did not alter the constrictor activity. Decreased constrictor activity was observed with human SFH cross-linked by glutaraldehyde treatment, or purified by affinity chromatography, and with bovine SFH purified by ultrafiltration and preparative HPLC. In isolated kidneys modified and unmodified SFH increased renal vascular resistance and decreased glomerular filtration rate with no morphologic evidence of tubular damage.

Animals↗

The systemic activation of platelets by Dacron grafts.

Dacron (polyester fiber), a stimulus to platelet aggregation in vitro, accumulates platelets to a greater extent in vivo than autogenous artery, polytetrafluoroethylene (PTFE) or human umbilical vein (HUV). We conducted a series of experiments using the ex vivo shunt in the baboon to determine whether or not systemic activation of platelet function was produced by a Dacron graft. Two 5 centimeter segments of 4 millimeter internal diameter graft materials were placed in series in the ex vivo shunt perfused at 25 milliliters per minute flow rate for two and one-half hours. Deposition of autologous Indium 111 labeled platelets was monitored. The ex vivo shunt procedures were divided into two groups, both with PTFE as the proximal graft: one with a distal Dacron graft (n = 21), the second with PTFE or HUV distally (n = 17). In this study, an increase in platelet deposition on the proximal PTFE graft represents systemic platelet activation caused by the distal graft. Increased platelet deposition on PTFE was noted at all time points in the presence of a Dacron graft (p less than 0.05). This property of Dacron has important clinical implications, potentially accelerating the progression of vascular disease, increasing the failure rate of composite grafts and subsequent arterial reconstruction.

Animals↗

Effects of plasma administration on gram negative shock in granulocytopenic dogs.

We studied the effect of an infusion of citrated plasma on the hemodynamic response and bacterial clearance of acutely septic dogs rendered severely neutropenic with cyclophosphamide. Two hours after a 5 X 10(9)/kg intravenous injection of E. coli, neutropenic control dogs infused with 20 ml/kg of normal saline became hypotensive and remained so for the next 2 hr. In contrast, the infusion of 20 ml/kg of citrated plasma after the initiation of bacteremia was followed by a significant (P less than .01) improvement in the mean arterial pressure (MAP), compared to saline-treated animals. The effect of citrated plasma administration on MAP was unrelated to bacterial clearance or to improvement in cardiac output but was associated with an increase in total peripheral resistance that was sustained for 2 hr after plasma infusion. The infusion of hyperimmune plasma from dogs previously immunized to core glycolipid antigen appeared to have no important advantage over normal plasma. At the doses of plasma that were given, a relatively higher arterial pH was the only observed significant difference (P less than .05) when immune plasma was compared to normal plasma. Resuscitation of septic neutropenic dogs with large volumes of plasma deserves further study with respect to the specific mechanisms responsible for its beneficial effect.

Agranulocytosis↗

A clinical experience with ADSOL preserved erythrocytes.

This study was undertaken to determine how ADSOL (adenine, glucose, mannitol and sodium chloride) preservative affects the 24 hour post-transfusion survival values of human erythrocytes during storage at 4 degrees C. for 35, 42 and 49 days. The results show that acceptable 24 hour post-transfusion survival values were observed only after storage at 4 degrees C. for 35 days.

Adenine↗

Autologous red blood cell reinfusion: effects on stress and fluid regulatory hormones during exercise in the heat.

This study assessed the effects of induced erythrocythemia on stress and fluid regulatory hormones during walking exercise in the heat. Six unacclimated male subjects received approximately 600 ml of a sterile saline solution containing 50% volume-to-volume of autologous erythrocytes. Three heat stress tests (HSTs) were attempted: one approximately 2 weeks prior to the reinfusion procedure, a second 48 h after the reinfusion procedure, and a third 1 week later, corresponding to 9 d subsequent to reinfusion. Each HST comprised three consecutive 45-min exercise and 15-min rest intervals (VO2 approximately 2.0 L.min-1, 1.56 m.s-1, 6% incline, 35 degrees C, 45% rh). Blood was withdrawn before the HST and 30 min into each exercise (EX) bout. In all three HST's plasma cortisol (PC) levels were significantly (p less than 0.01) reduced during the first EX bout compared to preexercise levels, and then progressively increased during the second and third EX intervals during HST 1. During HST 2 (48 h postinfusion), however, PC levels were significantly (p less than 0.05) reduced in two blood samples (EX 2, 3) compared to the same blood samples from HST-1 (preinfusion). Plasma renin activity (PRA) and aldosterone (ALD) were significantly (p less than 0.01) increased by the exercise/heat stress, but were unaffected by erythrocythemia either 48 h or 9 d subsequent to reinfusion. PRA and ALD were correlated (r = 0.84, p less than 0.001) under all conditions. We concluded from this study that acutely induced erythrocythemia reduced the stress response to consecutive exercise/heat intervals as manifested in PC responses during HST 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Morphology of cells grown in the CFU-GEMM tissue culture assay from mononuclear cells obtained from peripheral blood and bone marrow of normal volunteers.

In ten healthy volunteers studies were done to assess the morphology, immunocytology, and cytochemical properties of mononuclear hematopoietic stem cells isolated from normal human peripheral blood and bone marrow grown in semisolid matrix mixed lineage colony-forming unit (CFU-GEMM) culture. In three volunteers, peripheral blood and bone marrow samples were collected simultaneously; the progeny were remarkably similar in each of the three paired cultures, although macrophages were more numerous in the bone marrow cultures. Three peripheral blood samples were cultured following frozen storage with 10% DMSO at-150 degrees C for approximately 5 months. Megakaryopoiesis was present in each case, demonstrating the full hematopoietic potential of previously frozen peripheral blood mononuclear cells. Four other peripheral blood samples and one bone marrow sample were cultured and, in each case, cells of all hematopoietic cell lines were present. Bone marrow, peripheral blood mononuclear cells, and previously frozen peripheral blood mononuclear cells grown in the CFU-GEMM tissue culture assay showed the presence of granulocyte-macrophage, erythroid, and megakaryocytic cell lines.

Adult↗

Effects of nitroprusside and ketanserin upon pulmonary edema after acid injury.

Increased hydrostatic pressure and microvascular permeability after acid aspiration as causes of pulmonary and tracheobronchial edema were studied. Eighteen dogs were anesthetized and 3.0 milliliters per kilogram of 0.1 normal hydrochloride instilled into the trachea. After one hour, the platelet count decreased 47,500 per cubic millimeter (p less than 0.05) from base line levels of 221,400 per cubic millimeter and platelet serotonin stores decreased from 2.09 to 1.65 micrograms per 10(9) platelets (p less than 0.05). Mean pulmonary arterial pressure increased progressively from a base line value of 11 to 21 millimeters of mercury four hours after acid instillation (p less than 0.05). Mean arterial pressure fluctuated from a high of 143 millimeters of mercury to the final value, at four hours, of 119 millimeters of mercury. Ketanserin, a serotonin receptor antagonist, infused one hour after acid injury did not prevent release of platelet 5 hydroxytryptamine but led to a 24 per cent decrease in mean pulmonary arterial pressure from 13 to 10 millimeters of mercury (p less than 0.05) and an 11 per cent decrease in mean arterial pressure from 135 to 120 millimeters of mercury (p less than 0.05). Nitroprusside produced a 30 per cent decrease in mean arterial pressure, but only a 20 per cent decline in mean pulmonary arterial pressure (p less than 0.05). Four hours after acid was instilled, untreated dogs produced 129 milliliters of edema fluid from the endotracheal tube. In proportion to the relative decline in mean pulmonary arterial pressure, nitroprusside therapy reduced the volume of edema to 72 milliliters (p less than 0.05) and ketanserin to 52 milliliters (p less than 0.05). These results suggest that 5 hydroxytryptamine contributes to the pulmonary hypertension associated with acid injury and that the volume of edema formed may be directly related to the increase in the hydrostatic pressure.

Animals↗

Hemodynamic effects of different preparations of stroma free hemolysates in the isolated perfused rat kidney.

We have examined the effects of Stroma Free Hemolysate (SFH) solutions in the isolated perfused rat kidney. Three types of SFH, stored for 6 to 8 months at 4 degrees C, were tested: 1) unmodified, 2) glyoxalated and lightly cross linked and 3) pyridoxalated and polymerized. All three SFH solutions, added to the perfusate at a concentration of approximately 420 mg/100ml, increased renal vascular resistance (RVR) and reduced glomerular filtration rate (GFR). Unmodified, glyoxalated and lightly cross linked and pyridoxalated polymerized SFH resulted in a rise in RVR of 55%, 38% and 33% respectively and a fall in GFR of 42%, 57% and 83% respectively. In order to determine whether storage had altered the effect of SFH on renal function, one of the forms of SFH (glyoxalated and lightly cross linked) was studied only 4-6 weeks after preparation. While this preparation caused an increase in RVR of 41% it did not alter GFR; filtration fraction (FF) rose. However, after further storage of this preparation for 6-7 months, the solution resulted in a marked decrease in GFR of 47% as well as a rise in RVR of 23%. We conclude that three different SFH preparations resulted in marked vasoconstriction and reductions in GFR. These deleterious effects on renal hemodynamics were noted at a concentration of hemoglobin well below that necessary to effectively improve oxygen content. Storage of the SFH solutions may cause or contribute to their effects on renal function. SFH solutions intended for use as blood substitutes should be tested for vasoconstrictor activity.

Animals↗

Reduced coronary vasoconstrictor activity of hemoglobin solutions purified by ATP-agarose affinity chromatography.

Stroma-free hemoglobin (Hb) solutions are being developed as blood substitutes. We previously described coronary vasoconstrictor activity of Hb solutions prepared by conventional methods. In the present study we assessed the constrictor activity of unmodified and covalently modified Hb solutions purified by ATP-agarose affinity chromatography. The starting material was a red cell lysate, partially purified by ultrafiltration. Coronary constrictor activity was measured as increased perfusion pressure in isolated rabbit hearts perfused at constant coronary flow rate with buffer containing various concentrations of added Hb. The starting material increased perfusion pressure by 35 +/- 7 mmHg at 50 mg/dl. Purified Hb, retained by the affinity column, increased perfusion pressure by only 18 +/- 2 mmHg at 50 mg/dl. Hemoglobin covalently linked to ATP or pyridoxal phosphate, then purified by affinity chromatography, also had less constrictor activity than the starting material. Thus, a substance, removed by affinity chromatography but not by conventional purification, contributes to the vasoconstrictor activity of Hb solutions.

Adenosine Triphosphate↗

The effect of low molecular weight dextran on platelet deposition onto prosthetic materials.

Low molecular weight dextran (LMD) has recently been shown in a randomized, multicenter trial to improve early patency in difficult lower extremity vascular bypass. The question remained as to whether this effect was due to plasma volume expansion by LMD or to its effects on platelets and coagulation. To analyze this we have studied the effects of LMD on platelet-graft interactions using an ex vivo baboon shunt. Indium 111-labeled autologous platelet deposition on expanded polytetrafluoroethylene and knitted Dacron grafts was monitored at a flow rate of 25 ml/min for 21/2 hours. LMD was given by intravenous bolus at a dose of 5 ml/kg and was followed by a continuous infusion of 10 ml/hr. Flow through the shunt was started after the initial dextran bolus. Control studies were performed in a similar manner without dextran. An additional series of experiments was performed with a 5 to 10 ml/kg bolus of 5% human serum albumin to analyze the contribution of plasma volume expansion to platelet deposition in this model. The results revealed a significant (p less than 0.05) reduction in platelet deposition on both graft materials with the LMD infusion. No difference was seen between the control group and the albumin group. These studies provide direct in vivo evidence of the antiplatelet effect of LMD.

Albumins↗

Hypothermia-induced reversible platelet dysfunction.

Baboons that were subjected to systemic hypothermia at 32 C had an arm skin temperature of 27.3 C and bleeding time of 5.8 minutes. With local warming of the arm skin to 34 C, the bleeding time was 2.4 minutes. In normothermic baboons with arm skin temperature of 34.6 C, the bleeding time was 3.1 minutes. Local cooling of the arm skin to 27.6 C produced a bleeding time of 6.9 minutes. Increasing the skin temperature of the arm in hypothermic baboons to 38.9 C and in normothermic baboons to 40.1 C reduced bleeding times to 2.1 and 2.3 minutes, respectively. In both hypothermic and normothermic baboons there was a negative and significant correlation between the bleeding time and the arm skin temperature and the thromboxane B2 level in the shed blood obtained at the template bleeding time site. There was a significant positive correlation between the thromboxane B2 level in the shed blood and the arm skin temperature. Both in-vivo and in-vitro studies have shown that the production of thromboxane B2 by platelets is temperature-dependent, and that a cooling of skin temperature produces a reversible platelet dysfunction. Data also suggest that when a hypothermic patient bleeds without surgical cause, skin and wound temperature should be restored to normal before the administration of blood products that are not only expensive but may also transmit disease.

Animals↗