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Biomedical subjects

D L Carden

Publications and source records attributed to D L Carden.

At least 19 recordsLinked to original sources
PubMed1991

Oxidant-mediated, CD18-dependent microvascular dysfunction induced by complement-activated granulocytes.

To determine the mechanisms whereby complement-activated granulocytes induce microvascular dysfunction in skeletal muscle, we examined the effect of antineutrophil serum (ANS), IB4 (a monoclonal antibody that inhibits CD18-dependent neutrophil adherence), xanthine oxidase inhibition or inactivation, deferoxamine, and catalase on the increase in canine gracilis muscle microvascular permeability induced by intravascular administration of zymosan-activated plasma (ZAP). Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient (sigma) for total plasma proteins, and the extent of neutrophil infiltration was estimated by assessing muscle myeloperoxidase activity. ZAP infusion was associated with a marked increase in vascular permeability compared with control muscles that received no treatment or to muscles treated with zymosan heat-inactivated plasma (ZIP) (sigma = 0.51 +/- 0.04, 0.89 +/- 0.02, and 0.90 +/- 0.01, respectively). Estimates of sigma in animals rendered neutropenic with ANS, or treated with IB4, deferoxamine, or catalase before ZAP infusion were not significantly different from values obtained in control or ZIP-treated muscles (sigma = 0.96 +/- 0.02, 0.88 +/- 0.03, 0.85 +/- 0.02, and 0.79 +/- 0.01, respectively). However, xanthine oxidase inactivation or inhibition provided no protection from this ZAP-induced microvascular dysfunction (sigma = 0.58 +/- 0.02 and 0.58 +/- 0.01, respectively). In addition, neutropenia and inhibition of neutrophil adherence also prevented ZAP-induced increases in vascular resistance and tissue neutrophil infiltration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Activated neutrophils increase microvascular permeability in skeletal muscle: role of xanthine oxidase.

To determine the role of xanthine oxidase in the microvascular dysfunction produced by activated granulocytes, we examined the effect of xanthine oxidase depletion or inhibition on the increase in microvascular permeability produced by infusion of the neutrophil activator phorbol myristate acetate (PMA). Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in rat hindquarters subjected to PMA infusion in xanthine oxidase-replete and -depleted animals, in animals pretreated with the xanthine oxidase inhibitor oxypurinol, and in animals depleted of circulating neutrophils by pretreatment with antineutrophil serum (ANS). Xanthine oxidase depletion was accomplished by administration of a tungsten-supplemented (0.7 g/kg diet) molybdenum-deficient diet. In animals fed the tungsten diet, muscle total xanthine dehydrogenase plus xanthine oxidase activity was decreased to less than 10% of control values. Estimates of sigma averaged 0.84 +/- 0.04 in control hindquarters, whereas PMA infusion was associated with a marked increase in microvascular permeability (decrease in sigma to 0.68 +/- 0.03). PMA infusion also caused an increase in the amount of the radical-producing oxidase form of xanthine oxidase (from 3.9 +/- 0.05 to 5.6 +/- 0.4 mU/g wet wt). ANS pretreatment attenuated this permeability increase (sigma = 0.77 +/- 0.04) and diminished the rise in xanthine oxidase activity (4.9 +/- 0.5 mU/g wet wt). Xanthine oxidase depletion with the tungsten diet or pretreatment with oxypurinol had no effect on this neutrophil-mediated microvascular injury (sigma = 0.69 +/- 0.06 and 0.67 +/- 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Phalloidin attenuates postischemic neutrophil infiltration and increased microvascular permeability.

The aim of this study was to determine whether phalloidin (1 microM) or antamanide (1 microM), cyclic peptides that stabilize dense peripheral band and stress fiber F-actin in endothelium, would attenuate the increase in microvascular permeability induced by 4 h of ischemia and 30 min of reperfusion (I/R) in the isolated canine gracilis muscle. Changes in microvascular permeability (1 - sigma) were assessed by determining the solvent drag reflection coefficient for total plasma proteins (sigma) in muscles subjected to 4.5 h of continuous perfusion (nonischemic controls), I/R alone, I/R + phalloidin, or I/R + antamanide. Muscle neutrophil content was assessed by determination of myeloperoxidase (MPO) activity in tissue samples obtained at the end of the experiments. Fluorescent detection of nitrobenzoxadiazole-phallicidin in endothelial cell monolayers confirmed that phalloidin enters these cells. I/R was associated with marked increases in microvascular permeability and muscle neutrophil content (1 - sigma = 0.45 +/- 0.07; MPO = 8.9 +/- 0.5 units/g) relative to control (4.5 h continuous perfusion) preparations (1 - sigma = 0.12 +/- 0.03; MPO = 0.5 +/- 0.8 unit/g). These I/R-induced changes were largely prevented by administration of phalloidin (1 - sigma = 0.19 +/- 0.02; MPO = 0.8 +/- 0.4 U/g) or antamanide (1 - sigma = 0.07 +/- 0.11; MPO = 0.9 +/- 0.3 unit/g) at reperfusion. Similar results were obtained when phalloidin was administered before ischemia (1 - sigma = 0.24 +/- 0.04; MPO = 1.2 +/- 1.0 units/g). Although antamanide decreased superoxide production (by approximately 60%) and adherence to plastic (by approximately 75%) by activated neutrophils in vitro, phalloidin failed to alter these aspects of granulocyte function.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1990

Neutrophil-mediated microvascular dysfunction in postischemic canine skeletal muscle. Role of granulocyte adherence.

Recent studies implicate a role for granulocytes in the genesis of the microvascular and parenchymal cell dysfunction, which occurs upon reperfusion of ischemic tissues. Although the molecular mechanisms underlying this neutrophil-mediated injury are not completely understood, it is clear that an essential first step in granulocyte migration from the vascular lumen to the interstitial space is adherence to vascular endothelium. The purpose of this study was to determine whether prevention of neutrophil adherence with monoclonal antibody IB4 directed against the neutrophil CD11/CD18 glycoprotein adherence complex or neutrophil depletion with a specific polyclonal antineutrophil serum would attenuate the microvascular dysfunction seen in postischemic skeletal muscle. Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in isolated canine gracilis muscle subjected to ischemia/reperfusion, ischemia/reperfusion plus antineutrophil serum, or ischemia/reperfusion plus IB4. Estimates of sigma averaged 0.83 +/- 0.04 in nonischemic, control gracilis muscles, while ischemia/reperfusion was associated with a marked increase in vascular permeability (decrease in sigma to 0.54 +/- 0.04) and vascular resistance (increased by 135 +/- 41% over the control value). Prevention of neutrophil adherence or neutrophil depletion prevented this increase in vascular permeability (sigma = 0.80 +/- 0.03 and 1.01 +/- 0.06, respectively) and resistance (decrease of 16.51 +/- 8.0% and increase of 2.4 +/- 4.6% over control values, respectively). The results of this study suggest that neutrophils play a critical role in the genesis of microvascular dysfunction in postischemic skeletal muscle. Furthermore, neutrophil adherence to vascular endothelium appears to be a prerequisite for the production of this injury.

Animals↗
PubMed1989

The effect of cardiopulmonary bypass resuscitation on cardiac arrest induced lactic acidosis in dogs.

The adequacy of end organ blood flow following a cardiac arrest varies depending on the artificial reperfusion technique utilized and may critically affect patient outcome. Both oxygen consumption (VO2) and arterial lactate values have previously been used to assess tissue perfusion. Cardiopulmonary bypass resuscitation (CPB) is a reperfusion technique capable of providing near normal end organ blood flow. The purpose of this investigation was to study the effect of femoro-femoral veno-arterial CPB resuscitation compared to standard CPR on VO2 and arterial lactic acid values after a prolonged cardiac arrest. Ten mongrel dogs were electrically fibrillated and left in cardiopulmonary arrest without therapy for 12 min. Resuscitation was attempted according to a standardized protocol utilizing either CPB (n = 5) or standard external CPR (n = 5). Oxygen consumption values and arterial lactic acid samples were obtained at baseline, at timed intervals throughout resuscitation and after return of spontaneous circulation in successfully resuscitated dogs. Baseline hemodynamic and biochemical measurements were similar in both treatment groups (P greater than 0.05). Oxygen consumption (440 +/- 50 ml/min/M2) and mean arterial lactic acid values (7.44 +/- 2.25 mmol/l) were significantly higher at 1 min of resuscitation in CPB-treated dogs compared to dogs treated with CPR (60 +/- 10 ml/min/M2) (3.16 +/- 0.69 mmol/l) respectively (P less than 0.05). Mean arterial lactic acid values rose significantly at each sampling interval during CPR (P less than 0.05) but began to decrease after 5 min of resuscitation in the CPB animals and were not significantly different than baseline after 60 min of bypass (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗
PubMed1989

CPR-dependent consciousness: evidence for cardiac compression causing forward flow.

We present the case of a patient with cardiac arrest and resuscitation in whom, consistent with direct cardiac compression, large aortic-to-right atrial systolic pressure gradients occurred. Forward blood flow during CPR was sufficient for the patient to maintain consciousness. Although aortic-to-right atrial diastolic gradients adequate to maintain coronary perfusion in experimental models were generated, in our patient, cardiac function could not be restored and the resuscitation was ultimately unsuccessful.

Blood Circulation↗
PubMed1989

Hypoxic reperfusion attenuates postischemic microvascular injury.

The results of several recent studies have demonstrated that reactive oxygen metabolites are responsible for a major portion of ischemia/reperfusion (I/R) injury in skeletal muscle. Presumably, the cytotoxic oxidants are produced during reperfusion when molecular oxygen (the source of the reactive oxygen metabolites) is reintroduced to the tissues. The purpose of this study was to test the hypothesis that molecular oxygen must be provided at reperfusion to produce I/R injury in skeletal muscle. Isolated, maximally vasodilated (papaverine) canine gracilis muscles were reperfused, after 4 h of inflow occlusion, from reservoirs containing autologous blood equilibrated with either 95% O2-5% CO2 or 95% N2-5% CO2 gas mixtures. Arterial PO2 fell from approximately 120 mmHg to less than 3-5 mmHg, during the use of nitrogen. The solvent drag reflection coefficient for total plasma proteins (sigma f) and total vascular resistance was determined for the following conditions: control (no ischemia), reperfusion with oxygenated blood after 4 h ischemia; and reperfusion (after 4 h ischemia), first with anoxic blood and then oxygenated blood. Reperfusion with oxygenated blood, after 4 h of ischemia, significantly reduced solvent drag reflexion coefficient (sigma f) from 0.93 +/- 0.02 to 0.63 +/- 0.02, indicating a dramatic increase in vascular permeability. Total vascular resistance increased from 6.1 +/- 1.1 mmHg.ml-1.min.100 g during the preischemic period to 12.9 +/- 3.0 mmHg.ml-1.min.100 g during normoxic reperfusion. In muscles reperfused with anoxic blood, sigma f averaged 0.82 +/- 0.06, whereas vascular resistance increased by 56 +/- 13%.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1989

Role of iron in postischemic microvascular injury.

Iron-catalyzed formation of hydroxyl radicals has been postulated to occur during reperfusion of ischemic tissues. To assess the role of iron-catalyzed oxidant production in ischemia/reperfusion (I/R) injury to skeletal muscle, we examined the effects of deferoxamine (an iron chelator) and apotransferrin (an iron-binding protein) on the increased vascular permeability produced by I/R in isolated, pump-perfused rat hindquarters. Solvent drag reflection coefficients (sigma) were measured in hindquarters subjected to 2 h of ischemia and 30 min of reperfusion with either no pretreatment, pretreatment with 50 mg/kg deferoxamine, 200 mg/kg apotransferrin, or iron-loaded deferoxamine (50 mg/kg). I/R alone was associated with an increase in vascular permeability as indicated by the significantly lower estimates of sigma obtained after I/R (0.68 +/- 0.03) compared with those obtained in nonischemic preparations (0.82 +/- 0.02). Pretreatment with deferoxamine or apotransferrin attenuated this permeability increase (sigma = 0.83 +/- 0.03 and 0.86 +/- 0.02, respectively), whereas pretreatment with iron-loaded deferoxamine afforded no protection (sigma = 0.71 +/- 0.02). These findings are consistent with the hypothesis that iron-catalyzed oxidant production is important in the genesis of microvascular injury following I/R. Since the enzyme xanthine oxidase has been implicated as a major source of oxidants generated during reperfusion, we also measured tissue levels of xanthine oxidase and xanthine dehydrogenase in muscle samples obtained from the same hindquarters in which we measured permeability changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Role of xanthine oxidase in postischemic microvascular injury in skeletal muscle.

Previous reports indicate that allopurinol, a xanthine oxidase inhibitor, attenuates the microvascular injury produced by reperfusion of ischemic skeletal muscle. To further assess the role of xanthine oxidase in ischemia/reperfusion (I/R) injury, we examined the effect of xanthine oxidase depletion or inhibition on the increase in microvascular permeability produced by I/R. Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in rat hindquarters subjected to 2 h of ischemia and 30 min of reperfusion in xanthine oxidase-replete and -depleted animals and in animals pretreated with the xanthine oxidase inhibitor oxypurinol. Xanthine oxidase depletion was accomplished by administration of a tungsten-supplemented (0.7 g/kg diet), molybdenum-deficient diet. In animals fed the tungsten diet, muscle total xanthine dehydrogenase plus xanthine oxidase activity was decreased to less than 10% of control values. Estimates of sigma averaged 0.85 +/- 0.04 in nonischemic (continuous perfusion for 2.5 h) hindquarters, whereas muscle xanthine oxidase activity averaged 3.3 +/- 0.4 mU/g wet wt. I/R was associated with a marked decrease in sigma (0.54 +/- 0.02), whereas xanthine oxidase activity was increased to 5.8 +/- 0.5 mU/g wet wt. These results indicate that I/R produced a dramatic increase in vascular permeability coincident with an increase in muscle xanthine oxidase activity. Xanthine oxidase depletion with the tungsten diet or pretreatment with oxypurinol attenuated this permeability increase (sigma = 0.72 +/- 0.03 and 0.77 +/- 0.7, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Pneumonias.

Pneumonia is a common disease seen in Emergency Department patients and is caused by a wide range of pathogens. The clinical and laboratory data that help to provide a specific etiologic diagnosis of the pneumonia are reviewed. In addition, current recommendations for the treatment and hospitalization of patients with pneumonia are detailed.

Adult↗
PubMed1987

Cardiopulmonary bypass vs CPR as treatment for prolonged canine cardiopulmonary arrest.

Although in vitro studies have demonstrated functional recovery of neurons after prolonged ischemia, in vivo experience with patients resuscitated from cardiopulmonary arrest demonstrates much less cerebral resistance to global ischemia. The purpose of our investigation was to compare the effectiveness of femoro-femoral veno-arterial cardiopulmonary bypass (CPB) to standard cardiopulmonary resuscitation in the treatment of prolonged cardiopulmonary arrest. Ten mongrel dogs were electrically fibrillated and left in cardiopulmonary arrest without any therapy for 12 minutes. Subsequently, either CPB (n = 5) or CPR (n = 5) was initiated and resuscitation attempted according to a standardized protocol that included administration of the calcium channel blocker lidoflazine in an effort to optimize cerebral and myocardial recovery. If there was return of spontaneous circulation, the animal was managed in an intensive care setting with invasive hemodynamic monitoring and ventilatory support for up to nine hours. Neurologic function was graded using a standardized neurologic deficit scoring (NDS) system at 12 hours after insult and daily for one week or until death. Prearrest hemodynamic and metabolic parameters were comparable in both groups (P greater than .05). All CPB animals were resuscitated successfully and alive at 24 hours after insult as opposed to none in the CPR group (P less than .005). In addition, three of the CPB animals were neurologically normal at final grading with NDS scores of zero. The other two CPB animals had persistent severe neurologic impairment and a mean NDS score of 51%. Thus CPB is more effective than CPR in the treatment of prolonged cardiopulmonary arrest. The improved outcome probably results primarily from improvement in blood flow with CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Lactic acidosis during closed-chest CPR in dogs.

Survival after out-of-hospital cardiac arrest is intimately related to the time from cardiovascular collapse to the initiation of CPR, or downtime. Furthermore, the reperfusion technique that optimizes coronary and cerebral blood flow after cardiac arrest may also be dependent on downtime. Peak blood lactate levels have been shown to be unchanged throughout resuscitation and predictive of downtime in dogs subjected to cardiopulmonary arrest and open cardiac massage. The purpose of this study was to determine the course of arterial lactate levels in dogs subjected to a fibrillatory cardiopulmonary arrest and conventional closed-chest CPR (CCPR). Fourteen dogs were subjected to five minutes of cardiopulmonary arrest and 30 minutes of CCPR. Resuscitation was performed according to a standardized protocol. Arterial lactic acid samples were collected at timed intervals throughout the experiment. Mean arterial lactic acid levels increased significantly with each sampling interval during 30 minutes of CCPR (overall P less than .05). In nine dogs successfully resuscitated, there were no significant differences in mean arterial lactic acid levels after the return of spontaneous circulation (ROSC). Open-chest resuscitation after five minutes of ventricular fibrillation in dogs results in peak lactic acid levels that do not change significantly once internal cardiac massage is initiated. In contrast, CCPR in similarly arrested dogs does not appear to provide adequate tissue oxygenation and/or perfusion to prevent continuous lactic acid accumulation.

Acidosis, Lactic↗
PubMed1987

Selective venous hypercarbia during human CPR: implications regarding blood flow.

Thirty-five patients presenting to the emergency department in cardiopulmonary arrest had simultaneous measurement of central venous (cv) and arterial (a) blood gases during CPR with a pneumatic chest compressor and ventilator. The mean cv, arterial pH, and PCO2 values were markedly different (P less than .001). The mean pH gradient (pHa - pHcv) was .31 +/- .10 units and the mean PCO2 gradient (PcvCO2 - PaCO2) was 60.5 +/- 23.6 torr. This selective venous hypercarbia is probably due to a cardiac output that is inadequate to eliminate the CO2 produced from both residual aerobic metabolism and the buffering of anaerobically produced lactic acid. Central venous blood gases are probably a better reflection of actual tissue environment during prolonged cardiac arrest than are arterial blood gases.

Aged↗
PubMed1986

Aortic and right atrial pressures during standard and simultaneous compression and ventilation CPR in human beings.

Coronary perfusion pressure, as reflected by the diastolic aortic to right atrial (Ao-RA) pressure gradient, has been shown to correlate well with coronary blood flow during standard external CPR (SE-CPR) and is an important determinant of successful cardiac resuscitation. Few studies have documented such Ao-RA gradients in human beings, however. Twenty patients sustaining out-of-hospital cardiopulmonary arrests and basic cardiac life support were instrumented with thoracic aortic and right atrial catheters on arrival in the emergency department. The mean time from arrival in the ED to catheter placement was 16.5 +/- 6.0 minutes. With SE-CPR, peak systolic aortic and right atrial pressures were 73.7 +/- 20.2 mm Hg and 69.6 +/- 18.3 mm Hg, respectively. End diastolic aortic and right atrial pressures were 27.9 +/- 7.3 mm Hg and 20.3 +/- 7.2 mm Hg, respectively, with an end diastolic gradient of 7.9 +/- 9.1 mm Hg. Three patients had systolic Ao-RA gradients of more than 25 mm Hg, which is consistent with some cardiac compression as a mechanism of flow. Five patients also had one-minute trials of simultaneous compression and ventilation CPR (SCV-CPR). Ao-RA end diastolic gradients decreased in four of the five during SCV-CPR. No patient in this study was resuscitated successfully. We conclude that ED SE-CPR provides little coronary perfusion for victims of prehospital cardiac arrest. Although SCV-CPR has been shown to improve carotid blood flow in human beings, it appears to have an adverse effect on the already minimal myocardial perfusion provided by SE-CPR.

Aged↗
PubMed1986

Hyperkalemia during cardiac arrest and resuscitation in the canine model.

Although recent clinical reports have noted hypokalemia after resuscitation from cardiac arrest, extensive animal work indicates that potassium is released from cells during ischemia. This study was undertaken to define the changes that occur in serum potassium ion during cardiac arrest and resuscitation in a canine model. Fourteen dogs were subjected to 5 min of cardiac arrest followed by 30 min of closed-chest CPR (CCPR). Resuscitation was performed according to a standardized protocol. Serum potassium increased significantly (p less than .001) from baseline, remained elevated 5 min after return of spontaneous circulation (ROSC), but declined to baseline levels at 15 min post-ROSC. Increases in interstitial potassium would be expected to be even greater due to the poor exchange between interstitial and intravascular compartments during CCPR. Interstitial hyperkalemia may play a role in the genesis of wide-complex electromechanical dissociation and may explain the reported success of calcium chloride in treating this problem.

Animals↗
PubMed1985

Lactic acidosis as a predictor of downtime during cardiopulmonary arrest in dogs.

Studies have shown that over 50% of cardiovascular deaths occur before hospitalization. A major factor associated with survival in cases of out-of-hospital cardiac arrest is the time from cardiovascular collapse to the initiation of cardiopulmonary resuscitation (CPR) or "downtime." The purpose of this study was to determine whether blood lactate levels could be used to predict downtime in the canine cardiac arrest model. Femoral arterial and Swan-Ganz catheters were placed in 22 mongrel dogs, and ventricular fibrillation was electrically induced. The dogs remained in ventricular fibrillation without ventilation for 5, 10, 15, 30, or 60 minutes. After the predetermined fibrillation time, a left anterolateral thoracotomy was performed, and open-chest cardiac massage was begun. Arterial and mixed venous lactate levels were determined for every 5 minutes during 30 minutes of cardiopulmonary resuscitation. The correlation coefficient between the mixed venous and arterial lactate levels was 0.96 or greater during all stages of resuscitation. Peak serum lactate level increased linearly in relation to downtime. The increase in lactate level was not evident until after CPR was begun, and it remained at peak levels or decreased insignificantly, despite optimal open-chest CPR. Linear regression analysis revealed that 84% of the variability in serum lactate levels could be explained by downtime differences. In this model, blood lactate level is a reliable and objective measure of downtime and may be a useful indicator of the adequacy of CPR if levels decrease or remain stable. The clinical implications of this study lie with the use of blood lactate levels in the emergency department to guide the aggressiveness of resuscitative efforts.

Acidosis↗
PubMed1985

Central venous and mixed venous oxygen saturation: comparison during canine open-chest cardiopulmonary resuscitation.

Mixed venous oxygen saturation (MVO2) is a valuable parameter in monitoring critically ill patients because it serves as an index of the adequacy of the oxygen delivery system. Mixed venous oxygen saturation as reflected by the easily obtainable central venous oxygen saturation (CVO2) may prove useful during cardiopulmonary resuscitation (CPR) as an indicator of both the adequacy of varying CPR regimens and the efficacy of pharmacological interventions. This study investigates the relationship between CVO2 and MVO2 and its clinical usefulness during CPR. Swan-Ganz and central venous catheters were placed in 20 mongrel dogs. Ventricular fibrillation was then induced and, after predetermined downtimes ranging from 5 to 60 minutes, thoracotomy was performed, and open-chest bimanual cardiac massage was started. Central venous and mixed venous blood-gas samples were drawn every five minutes during a 30-minute period of CPR. The correlation between CVO2 and MVO2 was 0.8719 (P less than 0.001) before arrest but deteriorated at all times during CPR with values ranging from 0.1589 (P = 0.542) to 0.5781 (P = 0.024). Although statistically significant at times, the correlation between CVO2 and MVO2 during CPR is not consistently high enough to enable the routine substitution of CVO2 for MVO2 in assessing the oxygen delivery system.

Animals↗