R.D. Latimer

Endotoxin-induced organ injury

ObjectiveTo review the effects of endotoxemia on the major organ systems of the body and discuss potential mechanisms of tissue injury. DesignAppraisal of 60 articles representing a cross section of studies relating to in vivo and in vitro responses to endotoxin. Main MethodsCell cultures, isolated tissue preparations, animal and human studies. ResultsEndotoxemia results in the activation of numerous cellular and hematogenous mediators. These mediators range from prostaglandins, thromboxanes, and leukotrienes, to complement components. Tumor necrosis factor may be responsible for initiating many of the observed responses to endotoxin. Species and tissue specificity are a prominent feature of the response to endotoxin. ConclusionsNo single agent can yet be implicated as the common mediator of endotoxin-induced organ injury. Endotoxin initiates the elaboration of a cascade of secondary mediators that amplify the response to the initial insult. The relative importance of individual agents as mediators of the response to endotoxin varies with the experimental model studied. (Crit Care Med 1993; 21:S19-S24)

Comparison of clevidipine with sodium nitroprusside in the control of blood pressure after coronary artery surgery

Background and objective: We set out to compare the efficacy of clevidipine and sodium nitroprusside infusions in the control of blood pressure and the haemodynamic changes they produce in hypertensive patients after operation for elective coronary bypass grafting. Methods: Thirty patients were randomly allocated to receive either clevidipine or sodium nitroprusside after their mean arterial pressure (MAP) had reached >90 mmHg for at least 10 min in the postoperative period. The MAP was continuously measured and related to time. Thus, the efficacy of the drugs in controlling arterial pressure could be inversely related to the total area under the MAP-time curve outside a target MAP range of 70-80 mmHg normalized per hour (AUCMAP mmHg min h−1). Haemodynamic variables and the number of dose-rate adjustments required to maintain MAP were also studied. Results: There was no statistically significant difference in the efficacy (AUCMAP mmHg min h−1) of clevidipine (106 ± 25 mmHg min h−1) compared with sodium nitroprusside (101 ± 28 mmHg min h−1). Nor was any significant difference found in the total number of dose adjustments required to control MAP within the target range. The heart rate in patients receiving clevidipine increased less than in those given sodium nitroprusside. Stroke volume, central venous pressure and pulmonary artery pressure were significantly reduced upon administration of sodium nitroprusside but not of clevidipine. Conclusions: There was no significant difference between clevidipine and sodium nitroprusside in their efficacy in controlling MAP. The haemodynamic changes, including tachycardia, were less pronounced with clevidipine than with sodium nitroprusside.

A comparison of five heat and moisture exchangers

Five heat and moisture exchangers were investigated to compare their efficiency of humidification, their ability to filter bacterial spores and their various physical properties. The results are presented and the various mechanisms of heat and moisture exchange are reviewed. The Pall Ultipor BB50. because of its hydrophobic properties, has a slightly different action from heat and moisture exchangers already in use. The place of the Pall Ultipor BB50 in clinical practice is discussed.

Treatment of Perioperative Low Cardiac Output Syndrome

New approaches to the treatment of perioperative low cardiac output are considered. In particular, use of the phosphodiesterase III inhibitors and their cardiovascular actions are reviewed and contrasted with those of conventional inotropic agents. The increasing recognition of right-sided dysfunction is highlighted, and appropriate therapeutic strategies are considered. The increasing role of pulmonary-specific vasodilators such as inhaled nitric oxide is emphasized. Strategies to preserve right heart perfusion while producing pulmonary vasodilatation are discussed.

Management of donors for heart and heart–lung transplantation

The quality of donor organs will determine the quality of life for the recipient and the importance of optimal management of the multi‐organ donor is that the organs may benefit up to five, critically ill, patients. The basic principle is to maintain sufficient preload to minimise the need for inotropic support and it is recommended that all multiple organ donors should have central venous and arterial pressure monitoring in addition to adequate venous access. The importance of the choice of fluid for volume expansion and the management of the hormonal disturbances which follow brain death are considered.

The action of diaspirin cross-linked haemoglobin blood substitute on human arterial bypass conduits

BACKGROUND Immediately available blood substitutes could transform medicine. In coronary artery surgery, vasoconstriction induced by some of these agents could have serious implications. We have examined some of the vasoactive effects of one of these blood substitute, diaspirin cross-linked haemoglobin (DCLHb), on isolated rings of human arterial conduits. METHODS Sections of human left internal mammary artery (LIMA) and radial artery (RA) were cut into 3-mm rings, mounted in individual organ baths containing aerated (95% O(2)/5% CO(2)) Krebs-Heinseleit solution at 37 degrees C and attached to isometric strain gauge for measurements of tension. All rings were tested for the presence of endothelium by addition of carbachol to rings pre-contracted with phenylephrine. The relative importance of nitric oxide (NO) in contraction mediated by the addition of DCLHb was studied. RESULTS Carbachol relaxed phenylephrine precontracted LIMA by 72.3+/-1.7% and RA by 97+/-0.7% confirming the presence of a functional endothelium. Sodium nitroprusside (SNP) caused complete relaxation of LIMA with an EC(50) value of 2.0+/-0.1x10(-8) M and RA with an EC(50) value of 1. 9+/-0.1x10(8) M. In the presence of DCLHb (10(-7) M), carbachol-induced relaxation was significantly reduced to 46.3+/-0. 7% (P<0.01) and the BC(50) value for SNP relaxation increased to 1. 2+/-0.1x10(-7) M (P<0.01). DCLHb caused rings to contract in the absence of phenylephrine with EC(50) values of 1.6+/-0.1x10(-7) M (LIMA) and 1.8+/-0.1x10(-7) M (RA). Presence of L-NAME (300 microM) caused no alteration in DCLHb-induced contraction. CONCLUSION In this study of isolated rings of human vessels, DCLHb causes a significant reduction in relaxation mediated by carbachol and SNP, which is likely to be due to its ability to bind NO. However, it is possible that other mechanisms might contribute to the vasoconstrictor effects of DCLHb and these might be amenable to anti-vasospastic strategies.

Dopexamine hydrochloride: pharmacology and use in low cardiac output states.

T HE TERM “INOTROPE” is broadly used to describe agents that enhance cardiac performance, although the mechanism by which some of these drugs improve myocardial function may be attributable less to their effect on myocardial contractility than to the other hemodynamic changes that are associated with their use. In the treatment of cardiac failure, agents with pharmacodynamic profiles that combine relatively mild direct effects on the myocardium with those resulting from a relatively greater effect on preload and afterload offer potential benefits from the standpoint of myocardial energy use. This is of prime concern in both the acutely or chronically ischemic heart and following cardiopulmonary bypass (CPB) when cardiac failure can, on occasion, be ascribed more to unavailability of energy reserves than to persisting ischemia. Dopexamine hydrochloride, a synthetic analog of dopamine, is characterized by just such a profile of action and may offer a favorable alternative to the more established therapeutic regimens of dopamine and dobutamine. The pharmacology of dopexamine and its use in the treatment of chronic or postoperative cardiac failure is reviewed here.

Inhibitory effects of glibenclamide on the contraction of human arterial conduits used in coronary artery bypass surgery

Glibenclamide has been shown to inhibit prostanoid‐induced contraction in a number of blood vessel types. In this study, the effects of glibenclamide on the contraction of human peripheral arteries in response to both prostanoid and non‐prostanoid agonists were compared and possible mechanisms of action were investigated.

Management of low cardiac output syndrome after cardiac surgery using enoximone

This case report describes the use of enoximone, a potent phosphodiesterase F‐IV inhibitor with inotropic and vasodilator actions, to treat low output syndrome after cardiac surgery. The reduced cardiac output was unresponsive to a combination of inotropic drugs and intra‐aortic balloon counterpulsation was contraindicated. Cardiac output was increased dramatically by enoximone, but systemic vascular resistance and perfusion pressure remained low until the addition of metaraminol.

Effects of Intravenous Enoximone following Coronary Artery Bypass Surgery

The effects of intravenous enoximone were investigated in patients with reduced left ventricular ejection fraction following coronary artery bypass graft surgery. Pulmonary capillary wedge pressure was maintained at its original level during therapy. Results showed an improvement in cardiac index of approximately 35% and a reduction of systemic vascular resistance of approximately 30% in 10 out of 16 patients. In an attempt to explain the failure of 6 patients to respond to enoximone therapy, preliminary studies revealed that a repeat dose of enoximone may elicit a response. It is further suggested that postsurgical trauma may change the behaviour of the heart in response to this agent, perhaps due to a reduction in high-energy phosphate levels.