Plasmodium falciparum-induced kidney and liver dysfunction in malaria patients in Freetown; Sierra Leone

This study was undertaken to investigate the effect of Plasmodium falciparum infection on kidney and liver function parameters in malaria patients in Freetown; Sierra Leone. Blood samples taken from 64 malaria patients and 64 non-malaria volunteers at Abanita and Blue Shield Hospitals; Freetown Sierra Leone between January to April; 2009 were examined. Changes in serum biochemical parameters were analysed using normal range values as baseline. Serum bilirubin; alkaline phosphatase (ALP); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations were significantly elevated in falciparum malaria patients compared to their non-malaria counterparts which is an indication of defective liver function. Most of patients with falciparum malaria also have significantly high serum concentrations of urea; creatinine; sodium and potassium showing alteration in kidney function. This study suggests that malaria parasites could be responsible for derangement of kidney and liver functions in patients and could therefore contribute to organ damage in affected individuals if not treated

Chronic catecholamine depletion switches myocardium from carbohydrate to lipid utilisation.

PURPOSE: Chronic cardiac transplantation denervation (i.e., global sympathetic denervation with myocardial catecholamine depletion, plus parasympathetic denervation) is known to inhibit myocardial oxidation of glucose. It is not known whether this is due to increased utilization of lactate, lipid or ketone bodies. The purpose of the present study was to test the hypothesis that the extraction and contribution of blood-borne fatty acids (FA) to overall oxidative energy conversion is increased. METHODS: In anaesthetised dogs (control n = 6, cardiac denervated n = 6), we investigated fatty acid (FA) utilization. The studies were made at least four weeks after surgical cardiac denervation. Measurements were made of total FAs and with a radio-labelled tracer (U-14C palmitate). RESULTS: The contribution of FA utilisation to overall substrate oxidation rose from 31% (control) to 48% (cardiac denervated). The increase in the ratio (%) of CO2 production from palmitate oxidation to total CO2 production increased from 4.0 +/- 1.8 (control) to 10.6 +/- 5.8 (denervated, p = 0.04). The time from uptake of FA to release of CO2 product was unaltered. CONCLUSION: We conclude that the contribution of FA oxidation to overall energy conversion is increased in chronically denervated hearts, which is postulated to result from a decline in the active form of pyruvate dehydrogenase. This would appear to be a result of chronic catecholamine depletion.

Thrombosis in one coronary artery causes generalized coronary vasoconstriction in a dog model of unstable angina.

We investigated the effect of thrombosis in one coronary artery upon the vascular resistance of another coronary artery. In previous investigations, using an animal model of unstable angina, we have observed increased resistance downstream from thrombus within a left circumflex coronary artery (LCx) stenosis and vasoconstriction of collateral vessels from the left anterior descending artery (LAD) supplying the distal LCx vascular bed. In the present paper, we induced thrombosis within a stenosis of the LCx of 16 beagle dogs, and observed the changes in blood flow to the myocardium supplied by the LAD using the radioactive microsphere technique. This blood flow decreased with thrombosis (P = 0.005) in these animals, whereas it did not do so in three time-control experiments. The pressures across the coronary vascular bed, i.e. arterial pressure to coronary venous pressure (coronary sinus catheter), did not change. Thus the vascular resistance of the LAD bed increased significantly from 147 +/- ll.5 mmHg/ml/sec/g of tissue to 172 +/- 13.4 mmHg/ml/sec/g of tissue (P = 0.02). As the LAD territory is not perfused with blood from the artery containing thrombus, we conclude that the effect observed is caused either by release of vasoconstrictors from the thrombus into the general circulation, or by activation of a neural reflex vasoconstriction. The study suggests that unstable angina involving thrombosis in one coronary artery is a global coronary vascular disease.

Measurement of coronary collateral flow and resistance in the presence of an open critical stenosis, and the response to intra-arterial thrombosis.

OBJECTIVE: (1) Can one measure coronary collateral flow around an open critical stenosis? (2) Does intracoronary platelet thrombosis affect native coronary collateral vessels? METHODS: We measured regional myocardial blood flow by the radioactive microsphere technique in seven anaesthetised dogs with an ultrasonic flowmeter on the circumflex branch of the left coronary artery (LCx). Measurements were made (a) in a control period, (b) after induction of a tight stenosis on the LCx, and (c) after additional arterial damage at the stenosis to induce intraluminal thrombosis. Collateral flow was calculated from LCx tissue flow(in ml/min/g tissue) minus LCx flowmeter flow which is in ml/min. Therefore, it was necessary to use scaling by reference back to the control measurements and conversion to ml/min/g tissue equivalent. RESULTS: LCx stenosis induced collateral flow from the other coronary arteries into the LCx area of supply, which decreased (mean+/-S.E.) from 0.23+/-0.03 to 0.15+/-0.05 ml/min/g tissue with thrombosis. Collateral resistance correspondingly increased with thrombosis from 187.6+/-18. 2 to 1069+/-544 mmHg/ml/min/g (P<0.02). CONCLUSION: Coronary collateral flow around an open stenosis can be measured by reference back to control conditions. The coronary collaterals vasoconstrict in the presence of thrombosis even though they are in the stream of blood coming from normal coronary arteries.

Downstream resistance effects of intracoronary thrombosis in the stenosed canine coronary artery.

OBJECTIVE: The presence is well established in unstable angina of intracoronary thrombosis in a stenosed epicardial coronary artery. The effects of the thrombus formation on the distal microcirculation are however still unclear. METHODS: We adapted the Folts canine model of left circumflex coronary arterial stenosis and intracoronary thrombosis by the insertion of a pressure catheter distal to the stenosis and by the use of 15 microns radioactive microspheres for measurement of regional myocardial blood flow. This permitted measurement during circumflex artery occlusion of collateral flow, downstream vascular resistance and collateral resistance. RESULTS: Distal circumflex resistance, obtained by dividing the distal circumflex coronary pressure gradient by the collateral flow, significantly increased with thrombosis (94.47 +/- 35.72 to 120.06 +/- 34.47; p = 0.0018) mmHg/ml/min/g. Changes in collateral flow and resistance in the presence of thrombosis, during maximum ischaemic vasodilatation, were inconsistent. CONCLUSION: Thrombosis causes increased vascular resistance in the microcirculation distal to the site of injury. This may be of clinical relevance in unstable angina, characterised by episodes of thrombus growth and embolization, in which ischaemic episodes may be worsened by generalised downstream vascular changes.