Analysis of intestinal microvascular permeability associated with cardiopulmonary bypass

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with a generalized inflammatory response and splanchnic edema formation that are thought to be related to microvascular barrier injury. In particular, intestinal edema and dysfunction have been associated with sepsis and post-CPB complications. The purpose of this study was to measure the forces determining fluid flux induced by CPB across the intestinal microvascular barrier. MATERIALS AND METHODS: An anesthetized canine model was used for this study (n = 12). To determine mesenteric microvascular permeability, a mesenteric lymphatic was cannulated and mesenteric venous pressure was elevated to 33 +/- 1 mm Hg to reach a minimal lymph protein concentration (CL). With simultaneous measurement of plasma protein concentrations (CP), the reflection coefficient, sigma, was calculated using the formula: sigma = 1 - CL/CP. Capillary pressures (PC), lymph flow (QL), lymph protein flux, transvascular protein flux, and intestinal tissue water were all measured using standard techniques. Normothermic cardiopulmonary bypass with flows of 75-80 ml/kg/min was initiated after a steady state was achieved, and CPB was continued for 2 h and then discontinued. Measurements were repeated 30 min after CPB was discontinued. A second group (n = 5) was studied without mesenteric venous pressure elevation to evaluate the role of capillary pressure on the increased fluid flux seen with the initiation of CPB. RESULTS: Initiation of CPB was associated with an increase in intestinal microvascular permeability. Sigma decreased from 0.77 +/- 0.01 to 0.68 +/- 0.01 (P < 0.05) with the initiation of CPB. This corresponded with statistically significant increases in both transvascular protein flux from 310 +/- 22 to 465 +/- 39 ml/min at 30 min and intestinal tissue water from 82.8 +/- 0.7 to 84.3 +/- 0.5% after weaning from CPB. Capillary pressure did not significantly increase with the initiation of CPB. CONCLUSIONS: Initiation of CPB results in a moderate increase in intestinal microvascular permeability to protein and an increase in intestinal tissue water. The increases in tissue water are not due to increased capillary pressure. A better understanding of the microvascular changes associated with extracorporeal circulation will facilitate the search for clinical interventions to minimize the impact of CPB.     

Chronic digitalis administration alters mesenteric vascular reactivity

To characterize any digitalis-induced differences in intestinal blood flow autoregulation, we studied the circulatory responses of the rat intestine in control (n = 7) and chronically digitalized (n = 7) animals. Data were generated from denervated isoperfused small intestinal preparations. Arterial pressure, venous pressure, and oxygen consumption were continuously monitored. Determinations of intestinal blood flow allowed calculation of mesenteric vascular resistance and oxygen consumption. Animals underwent stepwise reductions in arterial pressure and acute venous hypertension (10 to 15 mm Hg). There were no differences in baseline hemodynamic or metabolic parameters in control (C) or digitalized (D) animals. Blood flow and oxygen consumption were autoregulated in both C and D rats until perfusion pressure decreased below 50 mm Hg. The response to acute venous hypertension was different. In D rats, venous hypertension resulted in increased vascular resistance (millimeters of mercury per milliliter per minute per 100 gm) [0.89 +/- 0.05 to 0.97 +/- 0.07; p less than 0.05], whereas C rats demonstrated no change [0.92 +/- 0.08 to 0.95 +/- 0.09]. The decrease in oxygen consumption in D rats (-14%) was slightly but significantly greater than that observed in C rats (-9%). Digitalized rats demonstrated a heightened myogenic response to acute venous hypertension with deleterious effects on vascular resistance and oxygen consumption. This reaction was intrinsic to the mesenteric circulation and not mediated by sympathetic nerves or central reflexes. Nonocclusive mesenteric ischemia in digitalized patients may reflect a similar abnormal response to the acute increases in portal pressure accompanying cardiac failure.     

The effect of hemodilution on blood flow regulation in normal and postischemic intestine

We investigated the effect of hemodilution on intestinal blood flow and oxygen consumption (VO2) in denervated rat small intestinal preparations. In one series of experiments, intestinal blood flow (IBF) and intestinal oxygen extraction (A-VO2) were measured during graded decreases in perfusion pressure. Control animals underwent consecutive studies without hemodilution; experimental animals were studied before and after isovolemic hemodilution. In a second series of experiments, normovolemic hemodilution was performed in experimental animals NH while hematocrit was maintained in controls, C. Preparations were then subjected to 30 min of complete ischemia followed by 30 min of reperfusion. Hemodilution (40.5 +/- 0.8% to 17.2 +/- 2.5%) decreased A-VO2 (3.9 +/- 0.5 to 2.1 +/- 0.4 ml/dl; P less than 0.05) but increased IBF (77.5 +/- 9.8 to 132.1 +/- 15.0 ml/min/100 gm; P less than 0.01). IBF was maintained to the limit of pressure:flow autoregulation (69 mmHg). Below this point, decreases in IBF were accompanied by increases in A-VO2 thus maintaining VO2. At a much lower "critical pressure" (42 mmHg) maximal oxygen extraction was reached and VO2 decreased with IBF. In the second series of experiments, hemodiluted animals (hematocrit 25 +/- 1%) studied during the reperfusion period maintained higher O2 consumption [30 min values (ml/min/100 gm): 4.8 +/- 0.9 NH vs 1.6 +/- 0.2 C, P less than 0.01] and A-VO2 difference [30 min values (vol%): 3.9 +/- 0.4 NH vs 2.1 +/- 0.4 C, P less than 0.005] than control animals (hct 33 +/- 2%). Hemodilution does not impair the intestine's ability to maintain O2 consumption during hypotension and hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved healing of extraperitoneal intestinal anastomoses in the early phase when surrounded by omentum

BACKGROUND: The extra-anatomical position of a cervical oesophagogastrostomy is a reason for impaired anastomotic healing, but transposition of the omentum that is covered with mesothelial cells may be a way to improve that. METHOD: This hypothesis was tested in a rat model. An end-to-end jejuno-jejunostomy was placed subcutaneously in group I (n = 29), subcutaneously surrounded by omentum in group II (n = 29) and intra-abdominally surrounded by omentum in group III (n = 20). After 3, 7 or 14 days, the rats were sacrificed and bursting pressure (BP) of the anastomosis or jejunum was measured and the hydroxyproline (HP) level was determined. RESULTS: In group I 5/29, in group II 2/29 and in group III 0/20 rats died following anastomotic leakage (nonsignificant) and were excluded from other measurements. BP was decreased after 3 days in group I (60+/-9 mm Hg) compared with group II (101+/-8 mm Hg) and group III (107+/-11 mm Hg) (p = 0.002). After 7 days, BP in groups I (122+/-10 mm Hg) and II (132+/-10 mm Hg) were lower as compared with group III (230+/-8 mm Hg) (p<0.001). Differences in HP levels were not statistically significant between the groups after 3, 7 and 14 days. CONCLUSION: The healing of intestinal anastomoses in an extraperitoneal position is improved in the early phase only when surrounded by omentum.     

The effect of fundoplication on the motility of the canine lower oesophageal sphincter

BACKGROUND: A canine model was used to define whether Nissen fundoplication inhibits gastro-oesophageal reflux by inhibiting transient lower oesophageal sphincter relaxations (TLOSR) or by creating a pressure barrier at the gastro-oesophageal junction. METHODS: Four surgical models were studied pre-operatively and postoperatively. These were: (i) the surgical mobilization required for fundoplication (sham fundoplication, n = 5); (ii) a standard fundoplication (n = 4); (iii) anterior and posterior myotomy of the lower oesophageal sphincter (LOS; cardiomyotomy, n = 4); and (iv) combined cardiomyotomy and fundoplication (n = 4). Each operative procedure was assessed for its effect on the incidence of TLOSR and gas reflux events, the mean LOS pressure and the LOS pressure profile during swallow events. RESULTS: Sham fundoplication reduced the rate of evoked TLOSR in response to gaseous gastric insufflation from 9.8+/-1.6/h (mean +/- SEM) to 5.4 +/-1.5/h. The mean LOS pressure was reduced from 25.1+/-2.6 to 18.5+/-2.1 mm Hg but nadir LOS pressure during swallowing was not altered. Nissen fundoplication virtually abolished evoked TLOSR from 10.4+/-1.2/h to 0.4+/-0.4/h, increased mean basal LOS pressure from 19.8+/-2.1 to 27.0+/-1.1 mm Hg and increased the nadir pressure on swallowing from 3.4+/-1.0 mm Hg to 14.4+/-1.0 mm Hg. Cardiomyotomy was associated with a near continuous leakage of gas across a chronically hypotensive LOS. Cardiomyotomy reduced the resting LOS pressure from 14.7+/-1.2 mm Hg to 2.3+/-1.0 mm Hg. Cardiomyotomy with fundoplication was associated with no loss of LOS competence. No gas venting episodes occurred either by passive leakage or by TLOSR. Cardiomyotomy with fundoplication was associated with a fall in mean LOS pressure from 14.3+/-1.5 mm Hg to 7.1+/-1.8 mm Hg but no LOS relaxation occurred during swallowing. CONCLUSION: Nissen fundoplication is highly effective in preventing reflux across a normal or chronically hypotensive LOS. Fundoplication results in a constant, measurable pressure barrier at the lower end of the oesophagus that is not due to a change in intrinsic LOS tone. Following fundoplication TLOSR are prevented by the constant low-pressure barrier.     

Superior protection in orthotopic rat lung transplantation with cyclic adenosine monophosphate and nitroglycerin-containing preservation solution.

BACKGROUND: Primary lung graft failure is common, and current lung preservation strategies are suboptimal. Because the decline in lung levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate during preservation could enhance adhesiveness of endothelial cells for leukocytes as well as increase vascular permeability and vasoconstriction, we hypothesized that buttressing these levels by means of a preservation solution would significantly improve lung preservation. METHODS: An orthotopic rat left lung transplantation model was used. Lungs were harvested from male Lewis rats and preserved for 6 hours at 4 degrees C with (1) Euro-Collins solution (n = 8); (2) University of Wisconsin solution (n = 8); (3) low-potassium dextran glucose solution (n = 8); (4) Columbia University solution (n = 8), which contains a cyclic adenosine monophosphate analog (dibutyryl cyclic adenosine monophosphate) and a nitric oxide donor (nitroglycerin) to buttress cyclic guanosine monophosphate levels; or (5) Columbia University solution without cyclic adenosine monophosphate or nitroglycerin (n = 8). PaO2, pulmonary vascular resistance, and recipient survival were evaluated 30 minutes after left lung transplantation and removal of the nontransplanted right lung from the pulmonary circulation. RESULTS: Among all groups studied, grafts stored with Columbia University solution demonstrated the highest Pa O2 (355 +/- 25 mm Hg for Columbia University solution versus 95 +/- 22 mm Hg for Euro-Collins solution, P <.01, 172 +/- 55 mm Hg for University of Wisconsin solution, P <.05, 76 +/- 15 mm Hg for low-potassium dextran glucose solution, P <.01, and 82 +/- 25 mm Hg for Columbia University solution without cyclic adenosine monophosphate or nitroglycerin, P <.01) and the lowest pulmonary vascular resistances (1 +/- 0.2 mm Hg * mL-1 * min-1 for Columbia University solution versus 12 +/- 4 mm Hg * mL-1 * min-1 for Euro-Collins solution, P <.01, 9 +/- 2 mm Hg * mL-1 * min-1 for University of Wisconsin solution, 14 +/- 6 mm Hg * mL-1 * min-1 for low-potassium dextran glucose solution, P <.01, and 8 +/- 2 mm Hg * mL-1 * min-1 for Columbia University solution without cyclic adenosine monophosphate and nitroglycerin). These functional and hemodynamic improvements provided by Columbia University solution were accompanied by decreased graft leukostasis and decreased recipient tumor necrosis factor alpha and interleukin 1alpha levels compared with the other groups. In toto, these improvements translated into superior survival among recipients of Columbia University solution-preserved grafts (100% for Columbia University solution, 37% for Euro-Collins solution, P <.01, 50% for University of Wisconsin solution, P <.05, 50% for low-potassium dextran glucose solution, P <.05, and 13% for Columbia University solution without cyclic adenosine monophosphate and nitroglycerin, P <.01). CONCLUSION: Nitroglycerin and cyclic adenosine monophosphate confer beneficial vascular effects that make Columbia University solution a superior lung preservation solution in a stringent rat lung transplantation model.     

In nonhuman primates intracarotid adenosine, but not sodium nitroprusside, increases cerebral blood flow.

Intracarotid infusion of short-acting vasodilators, such as adenosine and nitroprusside, in doses that lack significant systemic side effects, may permit controlled manipulation of cerebrovascular resistance. In this experiment we assessed changes in cerebral blood flow (CBF) after intracarotid infusion of nitroprusside and adenosine. The study was conducted on six adult baboons under isoflurane anesthesia and controlled ventilation. Intracarotid drug infusion protocol avoided hypotension during nitroprusside infusion and tested for autoregulatory vasoconstriction. CBF (intraarterial (133)Xe technique) was measured four times during infusions of 1) intracarotid saline, 2) IV phenylephrine (0.2 microg x kg(-1) x min(-1)) aimed to increase mean arterial pressure by 10-15 mm Hg, 3) IV phenylephrine and intracarotid nitroprusside (0.5 microg x kg(-1) x min(-1)), and 4) intracarotid adenosine (1 mg/min). IV phenylephrine increased mean arterial pressure (69 +/- 8 to 91 +/- 9 mm Hg, P < 0.0001, n = 6), and concurrent infusion of intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with IV phenylephrine or with concurrent infusion of IV phenylephrine and intracarotid nitroprusside. Intracarotid adenosine profoundly increased CBF (from 29 +/- 8 to 75 +/- 32 mL x 100 g(-1) x min(-1); P < 0.0001). In nonhuman primates, intracarotid adenosine increases CBF in doses that lack significant systemic side effects, whereas intracarotid nitroprusside has no effect. Intracarotid adenosine may be useful for manipulating cerebrovascular resistance and augmenting CBF during cerebral ischemia. IMPLICATIONS: Intraarterial (133)Xe cerebral blood flow (CBF) measurements suggest that intracarotid adenosine, in a dose that lacks significant systemic side effects, profoundly increases CBF, whereas nitroprusside has no effect.(5-12)     

Optimal time duration for low-pressure controlled reperfusion to efficiently protect ischemic rat heart

Previous studies have shown the capacity of low-pressure (LP) reperfusion to protect the ischemic heart. The present study sought to determine the optimal time for the application of LP reperfusion. Isolated rat hearts (n = 30) were exposed to 40 minutes of global warm ischemia followed by 70 minutes of reperfusion. Reperfusion was performed under LP (LP = 70 cm H(2)O) for 0 (control group), 5 (group LP-5), 10 (group LP-10), 30 (group LP-30), or 60 (group LP-60) minutes. Following the LP period the hearts were reperfused with normal pressure (100 cm H(2)O) until the end of reperfusion. Cardiac function was assessed during reperfusion using the Langendorff model. Myocardial necrosis was assessed by measuring LDH leakage in the coronary effluents. Functional recovery was reduced among the control and LP-5 groups with rate-pressure products (RPP) averaging 3788 +/- 499 and 5333 +/- 892 mm Hg/min, respectively. RPP was significantly improved in other groups with RPP averaging 7363 +/- 1159, 7441 +/- 863, and 7269 +/- 692 mm Hg/min in LP-10, LP-30, and LP-60 (P < .01). Similarly, necrosis measured by LDH leakage was significantly reduced in LP-10, LP-30, and LP-60 hearts (P < .01). This study demonstrated that LP reperfusion improves postischemic contractile dysfunction and attenuates necrosis when applied for at least 10 minutes.     

Polarized arrest with warm or cold adenosine/lidocaine blood cardioplegia is equivalent to hypothermic potassium blood cardioplegia

BACKGROUND: Hypothermic depolarizing hyperkalemic (K + 20 mEq/L) blood cardioplegia is the "gold standard" in cardiac surgery. K + has been associated with deleterious consequences, eg, intracellular calcium overload. This study tested the hypothesis that elective arrest in a polarized state with adenosine (400 micromol/L via adenosine triphosphate-sensitive potassium channel opening) and the Na + channel blocker lidocaine (750 micromol/L) as the arresting agents in blood cardioplegia provides cardioprotection comparable to standard hypothermic K + -blood cardioplegia. METHODS: Anesthetized dogs were placed on cardiopulmonary bypass and assigned to 1 of 3 groups receiving antegrade cardioplegia delivered every 20 minutes for 1 hour of arrest: cold (10 degrees C) K + -blood cardioplegia (n = 6), cold (10 degrees C) adenosine/lidocaine blood cardioplegia (n = 6), or warm (37 degrees C) adenosine/lidocaine blood cardioplegia (n = 6). After an hour of arrest, cardiopulmonary bypass was discontinued, and reperfusion was continued for 120 minutes. RESULTS: Time to arrest was longer with cold and warm adenosine/lidocaine blood cardioplegia (175 +/- 19 seconds and 143 +/- 19 seconds, respectively) compared with K + -blood cardioplegia (27 +/- 2 seconds; P < .001). Postcardioplegia left ventricular systolic function (slope of the end-systolic pressure/dimension relationship) was comparable among the 3 groups (K + -blood cardioplegia, 15.2 +/- 2.1 mm Hg/mm; cold adenosine/lidocaine blood cardioplegia, 15.9 +/- 3.4 mm Hg/mm; warm adenosine/lidocaine blood cardioplegia, 14.1 +/- 2.8 mm Hg/mm; P = .90). Plasma creatine kinase activity in cold and warm adenosine/lidocaine blood cardioplegia was similar to that in K + -blood cardioplegia at 120 minutes of reperfusion (cold adenosine/lidocaine blood cardioplegia, 11.5 +/- 2.1 IU/g protein; warm adenosine/lidocaine blood cardioplegia, 10.1 +/- 0.9 IU/g protein; K + -blood cardioplegia, 7.6 +/- 0.8 IU/g protein; P = .17). Postcardioplegia coronary artery endothelial function was preserved in all groups. CONCLUSIONS: Intermittent polarized arrest with warm or cold adenosine/lidocaine blood cardioplegia provided the same degree of myocardial protection as intermittent hypothermic K + -blood cardioplegia in normal hearts.     

Lower esophageal sphincter integrity is maintained during succinylcholine-induced fasciculations in dogs with "full" stomachs

During succinylcholine-induced muscle fasciculations, gastroesophageal barrier pressure in fasted adult dogs (n = 10) was compared by esophageal manometry with that in the same dogs with full stomachs. After fasting, fasciculations did not increase significantly either mean intragastric pressure (4.7 +/- 1.3 mm Hg before; 5.2 +/- 1.7 mm Hg during) or lower esophageal sphincter pressure (35.4 +/- 21.4 mm Hg before; 40.6 +/- 17.5 mm Hg during). Filling the dogs' stomachs with 300 mL of saline significantly increased both mean intragastric pressure (from 3.8 +/- 2.2 to 7.4 +/- 1.4 mm Hg) and mean lower esophageal sphincter pressure (from 20.2 +/- 6.8 to 28.6 +/- 14.8 mm Hg). Fasciculations did not produce a further increase in either mean intragastric or mean lower esophageal sphincter pressure. Most importantly, in all animals, under all conditions, gastroesophageal barrier pressure remained positive (range, 6.0-65.5 mm Hg) and therefore served as a barrier to passive regurgitation.     

The contribution of valves to saphenous vein graft resistance

Saphenous vein resistance influences graft flow rates and may affect graft patency in lower limb revascularization. To quantitate specifically the contribution of saphenous vein valves to this resistance, 10 human saphenous veins (mean length 68 cm, diameter 0.42 mm, and 5.2 valves per vein) were perfused with water under carefully controlled pressure gradients designed to simulate different peripheral resistances in the outflow bed. The Reynolds number was maintained at 350 to 600, within the physiologic range for in vivo grafts. Veins were perfused under both venous (10 mm Hg) and arterial (100 mm Hg) mean pressures to determine the effects of distension on the overall resistance of the conduit. The valves were bisected according to Leather's techniques and flow was measured in both directions, antegrade (simulating "reversed" grafts) and retrograde (simulating "in situ" grafts). Data (mean +/- standard error) were normalized to the baseline flow for each vein with intact valves and expressed as a percentage change. Data were analyzed by means of Student's t test (p less than 0.05). Baseline antegrade flow with intact valves averaged 71.0 +/- 3.0 ml/min at pressure gradients (delta P) of 10 mm Hg and 95.0 +/- 2.6 ml/min for delta P = 20 mm Hg. After valve incision, antegrade flow (reversed) increased an average of 29% at both pressure gradients. Retrograde flow (in situ) through the bisected valves was only 19% greater than baseline antegrade flow and was significantly less than antegrade flow through bisected valves. The difference is explained by theoretic considerations of stenosis area and orifice shape. The increases in flow did not correlate with vein length or diameter, nor did flow change with different distension pressures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Supplemental oxygen and carbon dioxide each increase subcutaneous and intestinal intramural oxygenation

Oxidative killing by neutrophils, a primary defense against surgical pathogens, is directly related to tissue oxygenation. We tested the hypothesis that supplemental inspired oxygen or mild hypercapnia (end-tidal PCO2 of 50 mm Hg) improves intestinal oxygenation. Pigs (25 +/- 2.5 kg) were used in 2 studies in random order: 1) Oxygen Study: 30% versus 100% inspired oxygen concentration at an end-tidal PCO2 of 40 mm Hg, and 2) Carbon Dioxide Study: end-tidal PCO2 of 30 mm Hg versus 50 mm Hg with 30% oxygen. Within each study, treatment order was randomized. Treatments were maintained for 1.5 h; measurements were averaged over the final hour. A tonometer inserted in the subcutaneous tissue of the left upper foreleg measured subcutaneous oxygen tension. Tonometers inserted into the intestinal wall measured intestinal intramural oxygen tension from the small and large intestines. Oxygen 100% administration doubled subcutaneous oxygen partial pressure (PO2) (57 +/- 10 to 107 +/- 48 mm Hg, P = 0.006) and large intestine intramural PO2 (53 +/- 14 to 118 +/- 72 mm Hg, P = 0.014); intramural PO2 increased 40% in the small intestine (37 +/- 10 to 52 +/- 25 mm Hg, P = 0.004). An end-tidal PCO2 of 50 mm Hg increased large intestinal PO2 approximately 16% (49 +/- 10 to 57 +/- 12 mm Hg, P = 0.039), whereas intramural PO2 increased by 45% in the small intestine (31 +/- 12 to 44 +/- 16 mm Hg, P = 0.002). Supplemental oxygen and mild hypercapnia each increased subcutaneous and intramural tissue PO2, with supplemental oxygen being most effective.     

Telemetric blood pressure monitoring in conscious rats before and after compression injury of spinal cord

Abnormal cardiovascular control after spinal cord injury (SCI) results in hypotension soon after injury. Later, paroxysmal hypertension and bradycardia in response to sensory stimulation below the level of injury develop in most people with SCI. In this study, we used a radiotelemetry system, in rats (n = 7), to investigate the effect of a clinically relevant compression model of SCI at T5 spinal segment on mean arterial pressure (MAP) and heart rate (HR) at rest and in response to colorectal distension. The transducers were implanted 1 month before clip compression (50-g) injury and continuous recording of MAP and HR was established for a period of 2.5 months. SCI was associated with hypotension (86+/-3 mm Hg) at 1 day after injury. In the following 2 days, MAP gradually returned to preinjury levels. By contrast, HR increased at 1 day after SCI and remained unchanged thereafter. Three days after SCI, colorectal distension caused an increase in MAP of 8+/-2 mm Hg accompanied by bradycardia (-18 bpm). One week after SCI, colorectal distension induced an increase in MAP of 9+/-2 mm Hg and bradycardia (-41 bpm). In the following days, the magnitude of reflex hypertension gradually increased, reaching 21+/-4 mm Hg at 1.5 months after SCI. In summary, our data show that resting MAP rapidly returns to control values after SCI. Episodic hypertension associated with autonomic dysreflexia can develop in rats within 1 month after incomplete SCI.     

Intramucosal-arterial Pco2 gradient does not reflect intestinal dysoxia in anemic hypoxia

BACKGROUND: An increase in intramucosal-arterial Pco2 gradient (DeltaPco2) might be caused by tissue hypoxia or by diminished blood flow. Our hypothesis was that DeltaPco2 should not be altered in anemic hypoxia with preserved blood flow. METHODS: In 18 anesthetized, mechanically ventilated sheep, oxygen transport was stepwise reduced by hemorrhage (hypovolemia, n = 9) or by hemorrhage and simultaneous dextran infusion (hemodilution, n = 9). RESULTS: Hypovolemia and hemodilution produced comparable decreases in systemic and intestinal oxygen transport and uptake. However, mixed venoarterial and mesenteric venoarterial Pco2 gradients and DeltaPco2 were significantly higher in hypovolemia than in hemodilution (25 +/- 5 vs. 10 +/- 2 mm Hg; 21 +/- 6 vs. 10 +/- 5 mm Hg; and 41 +/- 18 vs. 14 +/- 9 mm Hg, respectively; p < 0.01). CONCLUSION: DeltaPco2 did not reflect intestinal dysoxia during Vo2/Do2 dependency attributable to hemodilution. Blood flow seems to be the main determinant of DeltaPco2.     

Analysis of altered capillary pressure and permeability after thermal injury

In order to investigate the effects of thermal injury on microvascular hemodynamics and permeability, hindpaw arterial (PA), venous (PV), and capillary (PC) pressures, blood (QB) and lymph (QL) flows, and lymph (CL) and plasma (CP) total protein concentrations were measured before and for 3 hr after a 10-sec 100 degrees C scald burn in 11 dogs. Prior to injury in eight experiments (Group I--permeability analysis) venous pressure was elevated by outflow restriction until the minimal CL/CP was obtained. In three experiments (Group II--hemodynamic analysis) outflow was not restricted. Lymph and plasma protein fractions ranging in size from 37 to 120 A were measured using gradient gel electrophoresis and capillary equivalent pore sizes were calculated. In the early postburn period, PC increased from 24 +/- 2 (mean +/- SE) to 47 +/- 5 mm Hg (P less than 0.05) and precapillary resistance (RA) decreased from 6.6 +/- 0.2 to 2.5 +/- 0.2 mm Hg/ml/min/100 g (P less than 0.05) while postcapillary resistance (RV) remained unchanged. Pre- to postcapillary resistance (RA/RV) fell by 74%. The reflection coefficient for total proteins (calculated as sigma = 1 - CL/CP) decreased from 0.87 +/- 0.01 to 0.45 +/- 0.02 (P less than 0.01). Permeability of the postburn capillary endothelium was described by using two populations of equivalent pores. Preburn pore radii were 50 and 300 A with 13% of the capillary filtrate passing through the large pores. Pore radii increased after injury to 70 and 400 A with 49% of the filtrate passing through the large pores. The postburn total tissue filtration coefficient (Kf) increased to 2.4 times the control. Over the first 3 hr postburn, 53% of the increase in capillary filtration was attributable to increased capillary pressure and 47% to increased permeability. We conclude that the early rapid edema formation following thermal injury is the result of marked increases in both capillary filtration pressure and filtration through large nonsieving pores.     

The effect of external ocular compression on intraocular pressure following retrobulbar anesthesia

Thirty consecutive patients scheduled for cataract surgery were randomized to external compression with the Honan intraocular pressure (IOP) reducer or digital pressure. The average increase in IOP after retrobulbar injection of 4 ml of anesthetic was 6.20 mm Hg. This increase was followed by a rapid decline in IOP within the first 2 1/2 minutes, averaging 1.20 mm Hg +/- 0.70 below baseline level for the Honan group and 1.00 mm Hg +/- 0.96 below baseline level for the digital group. From 5 to 10 minutes after injection there was a more gradual decline in IOP that averaged 0.35 mm Hg/min in the Honan group and 0.36 mm Hg/min in the digital group. After 10 minutes of external compression the IOP was 5.73 mm Hg +/- 0.96 below baseline level in the Honan group and 4.67 mm Hg +/- 0.64 below baseline level in the digital group. No statistical difference between the IOP measurements of the two groups was observed at 2 1/2 minutes at 5 minutes, or at 10 minutes.     

Pulmonary artery systolic pressures estimated by echocardiogram vs cardiac catheterization in patients awaiting lung transplantation.

BACKGROUND: At many lung transplant centers, right heart catheterization and transthoracic echocardiogram are part of the routine pre-transplant evaluation to measure pulmonary pressures. Because decisions regarding single vs bilateral lung transplant procedures and the need for cardiopulmonary bypass are often made based on pulmonary artery systolic pressures, we sought to examine the relationship between estimated and measured pulmonary artery systolic pressures using echocardiogram and catheterization, respectively. METHODS: We retrospectively reviewed all patients in our program who had measured pulmonary hypertension (n = 57). Patients with both echocardiogram-estimated and catheterization-measured pulmonary artery systolic pressures performed within 2 weeks of each other were included (n = 19). We analyzed results for correlation and linear regression in the entire group and in the patients with primary pulmonary hypertension (n = 8) and pulmonary fibrosis (n = 8). RESULTS: In patients with primary pulmonary hypertension, pulmonary artery systolic pressure was 94 +/- 27 and 95 +/- 15 mm Hg by echocardiogram and catheterization, respectively, with r(2) = 0.11; in patients with pulmonary fibrosis, 57 +/- 23 and 58 +/- 12 mm Hg with r(2) = 0.22; and in the whole group, 76 +/- 29 and 75 +/- 23 mm Hg with r(2) = 0.50. Thirty-two additional patients had mean pulmonary artery systolic pressure = 48 +/- 16 mm Hg by catheterization but either had no evidence of tricuspid regurgitation by echocardiogram (n = 22) or the pulmonary artery systolic pressure could not be measured (n = 10). CONCLUSIONS: In patients with pulmonary hypertension awaiting transplant, pulmonary artery systolic pressures estimated by echocardiogram correspond but do not serve as an accurate predictive model of pulmonary artery systolic pressures measured by catheterization. Technical limitations of the echocardiogram in this patient population often preclude estimating pulmonary artery systolic pressure.     

Fundoplications resist reflux independent of in vivo anatomic relationships

BACKGROUND: Antireflux operations restore lower esophageal sphincter (LES) function and hiatal anatomy; however, the relative contributions are unclear. METHODS: We measured the competency of fundoplications, exclusive of in vivo variables, in gastroesophageal explants from 8 cadavers. Using a multichannel manometer, esophageal, LES, and intragastric pressures were recorded during transpyloric distension. Data were compared at baseline, and after Nissen (360 degrees) and Toupet (270 degrees) fundoplications. RESULTS: Before fundoplication, stomachs refluxed immediately upon distension. Nissen fundoplications never refluxed before gastric rupture (46.8 +/- 15.0 mm Hg). LES pressure averaged 2.0 +/- 0.5 times intragastric pressure during distension. Toupet fundoplications refluxed at intragastric pressure <2 mm Hg, then became competent until gastric rupture (49.9 +/- 15.0 mm Hg). LES pressure averaged 2.4 +/- 1.0 times intragastric pressure during distension. CONCLUSIONS: Nissen and Toupet fundoplications increase LES pressure linearly at 2 to 2.5 times intragastric pressure, independent of in vivo variables. Toupet fundoplication lacks the competency of Nissen fundoplication at low intragastric pressures.     

Vascular delay of the latissimus dorsi provides an early hemodynamic benefit in dynamic cardiomyoplasty.

OBJECTIVES: Dynamic cardiomyoplasty (CMP) as a surgical treatment for chronic heart failure improves functional class status for most patients. However, significant hemodynamic improvement with latissimus dorsi muscle (LDM) stimulation has not been consistent. The current protocols do not allow early LDM stimulation after CMP surgery. We hypothesized that vascular delay of LDM would increase myocardial assistance after CMP and allow early (48-h) LDM stimulation after CMP. METHODS: Mongrel dogs (n = 24) were divided in four groups: 1) controls (n = 6), single-stage CMP; 2) Group ES (n = 6), single-stage CMP with early LDM stimulation beginning 48 h, postoperatively; 3) Group VD (n = 6), vascular delay of the LDM followed by CMP without early LDM stimulation, and 4) Group VDES (n = 6), vascular delay of LDM (14-18 days), followed by CMP with early stimulation (48 h postoperatively). Two weeks after CMP, global cardiac dysfunction was induced by injecting microspheres into the left coronary artery. LDM-assisted (S) beats were compared with nonstimulated beats (NS) by measuring aortic pressure (AoP), LV pressure, aortic flow, and by calculating first derivative of LV contraction (+/-dP/dt), stroke volume (SV), and stroke work (SW). RESULTS: In ES, LDM stimulation had no effect on the hemodynamic parameters. In the other groups, LDM stimulation significantly (p < 0.05) increased AoP, LVP, dP/dt, SV, and SW. However, these increases were much larger in VD and VDES. In VD, LDM stimulation increased peak AoP by 21.5+/-3.8 mm Hg, LVP by 22.1+/-4.1 mm Hg, dP/dt by 512+/-163 mm Hg/sec, SV by 10.4+/-2.3 mL, and SW by 22.1+/-5.4 g/m(-1). Similarly, in VDES, LDM stimulation increased peak AoP by 24.1+/-4.7 mm Hg, LVP by 26.2+/-4.3 mm Hg, dP/dt by 619+/-47 mm Hg/sec, SV by 6.5+/-0.7 mL, and SW by 16.7+/-4.1 g/m(-1). CONCLUSIONS: In dogs with global LV dysfunction, CMP after vascular delay resulted in a significant improvement in hemodynamic function measured 2 weeks after surgery. This improvement was not provided by single-stage CMP with or without early stimulation. Vascular delay of the LDM before surgery may play an important role for early benefit after CMP, shorten the overall muscle training period, as well as increase hemodynamic response to LDM stimulation.     

Effects of dopamine on intestinal hemodynamics and motility during epidural analgesia in the cat

The effects of dopamine on intestinal blood flow (IBF) and intestinal contraction rate (ICR), and on mean arterial pressure (MAP) and heart rate (HR) were studied in eight cats before and during epidural analgesia (EDA). Before EDA, dopamine 5 and 10 micrograms.kg-1.min-1 had no effect on IBF, MAP and HR, but the higher infusion rate decreased ICR by 71 +/- 19% (mean +/- 1 s.e.mean) (P less than 0.01). EDA significantly increased IBF when intestinal arterial pressure was maintained at an unchanged level by means of a pump, and transiently increased ICR and intestinal tone, but reduced MAP by 46 +/- 8% (139 +/- 11 to 75 +/- 9 mmHg, P less than 0.01) and HR by 26 +/- 3% (248 +/- 7 to 184 +/- 8 beats.min-1, P less than 0.01). During EDA, dopamine increased IBF further, the response being similar at both infusion rates. 5 micrograms.kg-1.min-1 increased HR by 26 +/- 7 beats.min-1 (P less than 0.01) and MAP by 19 +/- 9 mmHg (ns). The corresponding values at 10 micrograms.kg-1.min-1 were 65 +/- 14 beats.min-1 (P less than 0.01) and 35 +/- 8 mmHg (P less than 0.01), respectively, Vascular autoregulation appeared to be unaffected by dopamine and EDA. The effect of dopamine on ICR was not significantly different to what was seen before EDA. It is concluded that the effects of dopamine on IBF, MAP and HR were markedly different during EDA as compared to before the block and that ICR was reduced by dopamine, while it was transiently increased by EDA.(ABSTRACT TRUNCATED AT 250 WORDS)