Combining nonpharmacologic therapies for advanced heart failure: the Münster experience with the assist device-defibrillator combination.

Implantable cardioverter defibrillators (ICDs) and ventricular assist devices (VADs) have been used as a bridge to cardiac transplantation. In selected patients, the combined implantation may be required. This study was motivated by a case of a 33-year-old female patient with giant cell myocarditis who died of ventricular tachyarrhythmias after having been placed on a VAD with which she had been treated on an out-of-hospital basis for a prolonged period of time. A subsequent retrospective analysis of our data showed that, of 73 patients who had to be bridged mechanically (54 Novacor, 12 TCI Heartmate, 4 Thoratec, 3 Medos) in our institution between 1993 and 1998, 10 patients had undergone defibrillator implantation either before (n = 8) or after (n = 2) implantation of a VAD. The cases are presented, and the feasibility of the combination therapy discussed.

Emergency versus elective/urgent left ventricular assist device implantation.

BACKGROUND: The risk and outcome in patients undergoing left ventricular assist device (LVAD) implantation on an emergency basis is still unclear. METHODS: Since April 1993, 40 patients received a Novacor and 8 patients a Heartmate LVAD in our institution. Patients with emergency LVAD placement were compared with the remainder in a retrospective manner. Parameters studied included underlying heart disease, preimplantation dysfunction of kidney, liver, lung, and cerebrum, interval of mechanical support, outcome, and complications. RESULTS: Patients with emergency LVAD placement predominantly were seen with postcardiotomy heart failure (47%) or acute myocarditis (20%) (group A) whereas elective and urgent candidates for LVAD implantation mainly had dilative cardiomyopathy (67%) or ischemic heart disease (30%) (group B). The incidence of secondary organ failure was significantly higher for all organs in group A patients (p < .01). Mean support interval in patients who underwent emergency LVAD implantation was lower (74+/-79 days vs 115+/-80 days), and fewer patients could be forwarded to heart transplantation in this group (22% vs 78%, p < .01). Moreover, bleeding complications were increased in group A (66% vs 30%, p < .01), but not thromboembolism and infection. CONCLUSION: In conclusion, the overall success rate after emergency LVAD implantation was lower, with bleeding being the most frequent complication. To achieve acceptable outcomes in disastrous situations, LVADs should be placed as early as possible.

Smoke inhalation causes a delayed increase in airway blood flow to primarily uninjured lung areas.

OBJECTIVE: Single lung inhalation injury causes tissue damage to the contralateral lung. We therefore examined airway blood flow after smoke inhalation in chronic instrumented sheep to get further information about the underlying pathophysiology. DESIGN/PATIENTS: The right lung and lower trachea of 5 animals were smoke-exposed, while their left lung was air-insufflated using a split ventilation technique. Three animals, where both lungs were only air-insufflated, served as controls. Blood flow to the airway was measured using a labeled microsphere technique. All animals were studied for 24 h following smoke inhalation. Then they were sacrificed and their tissues harvested. RESULTS: The airway blood flow to the smoke-exposed lung was elevated 11-fold immediately after inhalation injury. The bronchial blood flow to the air insufflated lung became significantly elevated 24 h post-smoke, although to a lesser extent. The control animals did not show any changes of bronchial blood flow during the observation time. CONCLUSIONS: Damage to one lung can lead to pathophysiologic changes in the contralateral lung. This response appears to be mediated by hematogenous factors.

Influence of enoximone on systemic and splanchnic oxygen utilization and endotoxin release following cardiopulmonary bypass.

OBJECTIVE: We investigated whether the administration of enoximone during and after cardiopulmonary bypass (CPB) improves splanchnic oxygen utilization and thereby gut mucosal integrity in humans by its vasodilating and inotropic properties. SETTING: Surgical intensive care unit (ICU) in a university hospital. DESIGN/PATIENTS: 21 patients (ASA III classification) scheduled for elective coronary artery bypass grafting were enrolled in the study. After induction of general anesthesia, patients were randomly assigned to received a bolus of 0.2 mg/kg enoximone, followed by 5 microg/kg per min (enoximone group), or followed by an equal volume of saline (NaCl group) during and 24 h after the surgical procedure. The following parameters were evaluated at different time intervals: systemic and pulmonary hemodynamics, blood gas analysis of arterial, mixed venous, and liver venous blood, venous and liver venous lactate level, venous and liver venous endotoxin level and intramucosal partial pressure of carbon dioxide for calculation of intramucosal pH (pHi). RESULTS: Enoximone raised cardiac output and oxygen delivery to higher levels than those observed in the NaCl group. In both groups, gastric pHi fell continuously during the study period. The values were significantly decreased 12 h following admission to the ICU. Endotoxin was not detectable at baseline. Both groups showed increased endotoxin levels, with the highest values during the first 6 h postoperatively. The hepatic venous endotoxin level was almost doubled in the NaCl group in comparison to the enoximone group. Endotoxin levels differed in the two groups 6 and 12 h after admission to the ICU. CONCLUSIONS: Improvement of oxygen delivery by enoximone did not prevent gastric mucosal acidosis following CPB. However, since the increase in endotoxin levels in liver venous blood was diminished by using enoximone, the drug seems to have a beneficial effect on tissue damage and barrier function of the gut.

Ventilation with positive end-expiratory airway pressure causes leukocyte retention in human lung.

We examined the effect of assisted ventilation with different positive end-expiratory airway pressures (PEEP) on pulmonary leukocyte retention in humans after cardiopulmonary bypass. Eight patients who underwent heart surgery were ventilated in the postoperative phase briefly with 10 (39.6 +/- 0.9 s) and 20 cmH2O (40.3 +/- 1.0 s) PEEP. Before, during, and after this ventilatory maneuver, blood was withdrawn simultaneously from catheters placed in the pulmonary and radial arteries for blood cell differentials. At the same time points, pulmonary and systemic hemodynamics were recorded. During PEEP ventilation, there was a four- (10 cmH2O PEEP) and an eightfold (20 cmH2O PEEP) increase in mixed venous-arterial leukocyte cell difference compared with baseline. This phenomenon was based mainly on a transpulmonary cell difference of polymorphonuclear cells. Likewise, the lymphocytes were entrapped in the pulmonary vasculature during PEEP ventilation. During the ventilatory maneuver, the pulmonary blood flow was significantly reduced; it was indexed by a declined cardiac output. We conclude that PEEP ventilation in the post-operative phase after cardiopulmonary bypass causes pulmonary polymorphonuclear cell entrapment. The most likely mechanism for this phenomenon is the compression of alveolar capillaries and reduced pulmonary blood flow in response to the raised alveolar pressure.

Mechanical alteration of blood flow in smoked and unsmoked lung areas after inhalation injury.

The degree of pulmonary perfusion may have an important role in the pathogenesis of inhalation injury. We studied this in sheep that had only one lung exposed to smoke. The right lung and upper airway of 12 chronically instrumented sheep were insufflated with cotton smoke. In six animals, the left pulmonary artery was occluded between 4 and 10 h after smoke insufflation. All animals were studied for 24 h and then killed, and lung tissue was harvested. The smoked as well as the air-insufflated lung of all animals showed an increase in wet-to-dry weight ratio and tissue conjugated dienes (products of lipid peroxidation). Neither the intermittent blood flow increase to the smoked lung nor the simultaneous blood flow reduction with a concomitant polymorphonuclear neutrophil entrapment in the air-insufflated lung significantly affected the histopathological outcome of the respective lung. We conclude that tissue damage after inhalation injury cannot be diminished by increasing the flow to smoked areas. Ischemia-reperfusion injury does not have a major role in the lung damage seen with inhalation injury.

Postburn gastrointestinal vasoconstriction increases bacterial and endotoxin translocation.

Splanchnic ischemia has been associated with bacterial translocation and increased endotoxin absorption from the gut. To study the effects of major burn on splanchnic circulation, minipigs were randomized to receive 40% flame burn and Parkland resuscitation or sham burn and maintenance fluids. Total and fractionated blood flow, O2 delivery and consumption, mucosal pH of the intestine, and endotoxin levels in the superior mesenteric vein were measured for 48 h, and then abdominal organs were harvested for bacteriological culture and histopathological analysis. Total mesenteric blood flow and fractionated blood flow to the mucosa-submucosa of the jejunum, cecum, and colon decreased 2 and 4 h postburn. Although mesenteric O2 consumption was unchanged, mesenteric O2 delivery and intestinal mucosal pH were decreased during the early postburn period. Concomitantly, endotoxin levels in the superior mesenteric vein were significantly elevated during the first 8 h postburn. The bacteriological cultures of the systemic tissue samples showed increased bacterial translocation in the burn group. After major burns, there is a transient selective splanchnic vasoconstriction, which is associated with intestinal mucosal acidosis and increased incidence of bacterial translocation and endotoxin absorption from the gut.

Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep.

Endotoxin [lipopolysaccharide (LPS)] has been reported to reduce hypoxic pulmonary vasoconstriction and thus increases venous admixture. The time course of this failure of pulmonary blood flow regulation was investigated in six chronically instrumented unanesthetized sheep after infusion of Escherichia coli LPS (1 microgram/kg). The change in left pulmonary arterial blood flow (LPBF, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left and right lungs) was compared before and at various time intervals after the administration of LPS. During baseline conditions, LPBF was 33% of total cardiac output and decreased to 15% when the left lung was ventilated with a hypoxic gas mixture. One hour after endotoxin infusion, LPBF remained at 33% of total cardiac output yet only decreased to 28% during the hypoxic challenge. The response to one-lung hypoxia was still significantly depressed 10 h post-LPS administration. It is concluded that hypoxic pulmonary vasoconstriction is almost completely abolished for a prolonged time period after a small dose of LPS.

Pulmonary hemodynamics and tissue damage after one lung infusion of Pseudomonas aeruginosa in sheep.

The relative roles of hematogenous mediators and direct bacterial toxicity due to phagocytosis by pulmonary intravascular macrophages were determined by selective bacterial infusion into the left pulmonary artery and comparison of right and left lungs at 24 h. Chronically instrumented sheep received 15-min pulmonary arterial infusions of live Pseudomonas aeruginosa (0.35-2.9 x 10(9), n = 6) or saline (n = 5). The saline group demonstrated stable cardiopulmonary function over time. Left lung blood flow, measured by Doppler flow probe, decreased 15 min into the bacterial infusion, with a concomitant sevenfold increase in left lung pulmonary vascular resistance index. The right lung pulmonary vascular resistance index doubled at 1 h, in association with increased plasma thromboxane B2 levels. An increase in cardiac index and decrease in systemic vascular resistance occurred at 12 h. The wet-to-dry weight ratio of the Pseudomonas-infused left lung was increased compared with that of the sham-infused lung. The tissue count of neutrophils in the lungs was doubled in both sides, but neutrophils on the left were more degranulated. The left lung tissue damage was caused by direct bacterial toxicity, including activation of phagocytic cells. Hematogenous mediators induced pulmonary and systemic hemodynamic changes and right lung neutrophil sequestration, but they did not damage the noninfused lung.

Mesenteric lymphadenectomy prevents postburn systemic spread of translocated bacteria.

We investigated the role of mesenteric lymph nodes in postburn systemic spread of intestinal bacteria. Group 1 minipigs (n=8) had a 40% third-degree burn. Group 2 minipigs (n=7) had the same burn injury, but their mesenteric lymph nodes were removed immediately after burn. Group 3 minipigs (n=8) had sham burn, and group 4 minipigs (n=6) had mesenteric lymph node removal under anesthesia. All minipigs were killed at 48 hours, and tissues were harvested for bacteriological culture. Group 1 showed a large number of positive cultures from several of the systemic organs. Group 2 demonstrated no positive cultures in any of the tissues except the peritoneal fluid. These data suggest that bacterial translocation occurs mainly via mesenteric lymphatics to mesenteric lymph nodes and, thence, into other systemic tissue. After major burns, mesenteric lymph nodes may become an additional focus of infection.

Neonatal mechanical bridging to total orthotopic heart transplantation.

BACKGROUND: Until recently, newborns with medically intractable cardiac failure caused by congenital malformations were mostly doomed to death because of the severity of the disease, which precludes a palliative operation, or because of fatal deterioration before availability of a suitable donor heart. METHODS: The recently developed paracorporeal pneumatically driven Medos HIA ventricular assist device offers a therapeutic option for these small infants because it is manufactured in various sizes and is even suitable for cardiac assistance in neonates with a body surface area less than 0.3 m2. RESULTS: We report our initial experience with this device, which we used for univentricular bridging to total orthotopic cardiac transplantation in 3 infants. The device was inserted to support the left ventricle in two instances and to support the right heart in one. Successful bridging to transplantation was achieved in 2 infants for periods of 2 and 7 weeks. CONCLUSIONS: Our experience demonstrates the feasibility of univentricular mechanical support followed by successful cardiac transplantation in infants and newborns.

Cardiac pacemaker infection: surgical management with and without extracorporeal circulation.

BACKGROUND: Pacemaker infections are rare, but serious complications of pacemaker therapy. The generator pocket, the pacing leads, or both may be involved. METHODS: We report on 12 patients with infected pacemaker systems. Four patients suffered from localized generator pocket infections, 6 had infected leads, and 2 patients had both. Pacemaker systems were completely removed in all patients. When the infection was limited to the generator pocket, the pacemaker system was removed at the original implantation site. Extracorporeal circulation was employed for the explantation of infected pacing leads. RESULTS: No complications occurred in patients with localized generator pocket infections. One patient with infected leads who was preoperatively already in a serious clinical condition died of septic shock in the early postoperative period; another patient died of pulmonary complications after tricuspid valve replacement 14 months after pacemaker explantation. No recurrent infections were observed. CONCLUSIONS: Explantation of the complete pacemaker system has proved a reliable method to eradicate infection. Complications have been rare, except in patients in a critically ill state who undergo cardiopulmonary bypass.

Halothane markedly reduces mesenteric blood flow but does not impair gut mucosal oxygenation in pigs.

We investigated the effect of halothane on in mesenteric blood flow and gut mucosal oxygenation. Pittman-Moore mini-pigs (n = 6) were chronically instrumented with aortic, pulmonary arterial (Swan-Ganz), and mesenteric venous catheters and an intestinal tonometer. Blood flow in the superior mesenteric artery was measured with an ultrasonic flow probe. On the day of the experiment, data were obtained before and during halothane administration (1.5% end-tidal). Halothane caused a marked decrease in mesenteric blood flow, associated with an increase in mesenteric vascular resistance. Likewise mesenteric oxygen delivery and consumption were significantly decreased under halothane, while the oxygen extraction rate of the intestine was not significantly changed. There was no significant change in intramucosal gut pH after halothane administration, which indicates that an adequate mucosal tissue oxygenation was maintained. We conclude that the marked halothane-induced reduction in mesenteric blood flow did not seem to impair the oxygenation of the gut mucosa in our experimental model.

Thromboxane receptor blockade with BM 13,177 following toxic airway damage by smoke inhalation in sheep.

Thromboxane may play an important role in the pathogenesis of smoked mediated injury. We studied this possibility in 13 chronically instrumented sheep, which had the left lung exposed to smoke. BM 13,177, a thromboxane receptor antagonist, was given intravenously to six animals prior to smoke inhalation and during the experimental period. Seven animals received the vehicle. All animals were studied for 24 h under ventilatory support, then killed prior to harvesting lung tissue. Airway peak and plateau pressures in the vehicle-treated animals were elevated by 27% and 25% from baseline at 24 h post smoke inhalation. Concomitantly, the left pulmonary vascular resistance index rose continuously throughout the study period (baseline = 822 +/- 58; 24 h = 1819 +/- 84 dyn.s.cm-5.m2).BM 13,177 treatment completely prevented the rise in airway pressure, while the left pulmonary vascular resistance index was significantly attenuated (baseline = 726 +/- 79; 24 h = 1470 +/- 158 dyn.s.cm-5.m2) resulting in a significantly higher percentage of cardiac output being delivered to the smoked lung, compared to vehicle-treated animals. Thromboxane receptor blockade did not prevent smoke induced pulmonary edema formation. There was likewise no effect of BM 13,177 on the systemic hemodynamic changes seen following smoke inhalation. There was a decrease in cardiac index and an increase in systemic vascular resistance index in both groups. We conclude that smoke induced changes in airway and pulmonary vascular resistances may be mediated by thromboxanes. However, thromboxanes appear to play no role in the development of pulmonary edema and elevation of systemic vascular resistance following smoke inhalation injury.

Plasma copper and iron changes in sheep after left lung inhalation injury: effect of the thromboxane antagonist BM 13.177 (Solutroban).

A significant decline in plasma concentrations of copper and iron were observed in sheep exposed to preferential smoke inhalation of the left lung. The decline was evident 30 minutes after smoke inhalation, and the levels of both trace metals persisted at quite low levels for up to the 18-hour time interval after injury. From that time a gradual recover for copper but not for iron levels was observed so that by 24 hours the levels of copper were in the same range of those at baseline. Copper and iron levels showed an inverse correlation to airway peak and plateau pressures and left lung vascular resistance index and a direct correlation to left lung blood flow. Administration of BM 13.177 (Solutroban), a thromboxane antagonist, before exposure to smoke inhalation protected the sheep from the decline of copper and iron levels in plasma. In these animals airway peak and plateau pressure, left lung vascular resistance, and blood flow were also unmodified. Lipid peroxidation of the lung tissue by oxygen free radicals were lower than in those animals that did not receive BM 13.177. There was likewise a tendency of a decreased wet-to-dry weight ratios in the animals treated with BM 13.177. BM 13.177 treatment in an inhalation injury model might partly protect lung damage and parallels unchanged plasma copper and iron levels. The plasma copper and iron may therefore be an indicator of acute lung damage.

Endoscopic laser flowmetry: a valid method for detection and quantitative analysis of inhalation injury.

Hyperemia of the tracheobronchial area is a major sign of inhalation injury. However, this is usually a qualitative symptom, without quantitative measurement. We have developed a technique to diagnose inhalation injury and to analyze damaged areas quantitatively with laser-doppler flowmetry. In chronically instrumented sheep (N = 10), the tissue blood flow in the wall of second generation bronchi was determined with an endoscopic flowmeter probe. After baseline data had been obtained, the right lung was exposed to smoke in seven animals. Three sham-smoked animals underwent the same procedure, but without actual smoke. The bronchial blood flow was measured again 30 minutes after insufflation in both groups. Inhalation injury caused a significant increase in flow, from 35.1 +/- 2.6 to 51.7 +/- 2.1 ml/min.100 gm tissue in the airway of the smoked lungs but not in the control lungs. This increase correlated with an increase in the carboxyhemoglobin level (r = 0.87). The sham-smoked animals showed no change in bronchial blood flow. A valid technique for diagnosing inhalation injury in the early phase and a quantitative analysis of injured areas has been demonstrated.

Carbon monoxide and pulmonary circulation in an ovine model.

The direct pulmonary vasoconstrictive effects of inhaled carbon monoxide were evaluated in chronically instrumented and anesthetized sheep (1.7% halothane in air) (n = 8). The response to carbon monoxide (2%), which was applied for 8 minutes through a double-lumen tube alternately to the left or right lung of each animal, was compared with baseline values. The induced carboxyhemoglobin level (65%) led to increases in cardiac output, pulmonary arterial pressure, stroke volume index, and heart rate. Systemic vascular resistance decreased, and pulmonary vascular resistance and mean arterial pressure were unchanged. The changes in pressure and flow were equivalent no matter which lung was exposed to carbon monoxide. No diversion of blood from one lung to the other was observed during the test period. We conclude that carbon monoxide does not have a direct pulmonary vasoconstrictive effect. The increase in pulmonary arterial pressure is a result of the decrease in mixed venous oxygen content (stimulus for hypoxic pulmonary vasoconstriction) and the increase in cardiac output.

The effect of dopamine on pulmonary hemodynamics and tissue damage after inhalation injury in an ovine model.

Hypoxic pulmonary vasoconstriction and reduced blood flow occur as a result of smoke inhalation. The aim of this study was to investigate how the amelioration of blood flow reduction by the vasodilator dopamine affects histopathologic outcome. We exposed the left lungs of chronically instrumented sheep (n = 12) to smoke, awakened them, and studied them for 24 hours. Six hours after inhalation injury, the sheep received randomized infusions of dopamine (9 micrograms/kg/min) or equal volumes of 0.9% saline solution. Pulmonary resistance in the left lungs of animals in the group that received saline solution rose continuously throughout the study period (624 +/- 48 dyne.sec.cm-5/m2 to 1747 +/- 140 dyne.sec.cm-5/m2, baseline to 24 hours after injury). Dopamine treatment caused a significantly lower vascular resistance in the injured lung than did saline solution between 8 and 24 hours after injury. The histologic evaluation of the injured lungs showed epithelial necrosis and cast formation in both groups in addition to an increased wet/dry ratio. No difference in lung injury between the groups could be distinguished. We conclude that the amelioration of blood flow reduction by treatment with dopamine in the lungs that were exposed to smoke did not affect pulmonary damage after inhalation injury.

Effects of enflurane and isoflurane on splanchnic oxygenation in humans.

STUDY OBJECTIVES: To determine the effects of enflurane and isoflurane on hepatic venous oxygen saturation (ShvO2) and splanchnic oxygen (O2) extraction. To measure hemodynamic parameters and ShvO2, mixed venous, and arterial lactate concentrations during enflurane and isoflurane anesthesia. DESIGN: Randomized, prospective study. SETTING: University hospital. PATIENTS: 20 ASA physical status I, II, and III adults, who underwent major abdominal surgery requiring mechanical ventilation a few hours postoperatively. INTERVENTIONS: After placement of catheters in the pulmonary artery, radial artery, peripheral and right hepatic vein, one hour postoperatively either enflurane or isoflurane was applied at different minimum alveolar concentration (MAC) of 0.5, 1.0, and 1.5 in a randomized order. MEASUREMENTS AND MAIN RESULTS: Before and 10 minutes after administration of each desired end-expiratory anesthetic concentration, the following parameters were determined: hemodynamic parameters, arterial (SaO2), mixed venous (SvO2), and hepatic venous oxygen saturations, systemic and splanchnic O2 extraction, arterial, mixed venous, and hepatic venous lactate concentrations. Cardiac output (CO) and mean arterial pressure (MAP) decreased in a dose dependent manner. SaO2, SvO2, and systemic O2 extraction remained unchanged with enflurane and isoflurane anesthesia. In the enflurane group, but not in the isoflurane group, ShvO2 decreased with increasing inhalational concentrations. This decrease in ShvO2 reflected an increase in splanchnic O2 extraction with enflurane; in contrast to isoflurane. CONCLUSIONS: Enflurane causes a decrease in ShvO2, which indicates an impairment of splanchnic perfusion corresponding to the reduction in CO and MAP in a dose-dependent manner. Isoflurane maintains splanchnic perfusion in contrast to enflurane.