Fermented lactotripeptides-containing milk lowers daytime blood pressure in high normal-to-mild hypertensive subjects.

This study shows that consumption of fermented lactotripeptides (LTPs)-containing milk may have an acute daytime effect on blood pressure that appeared sustained with daily intake over a period of 4 weeks. Angiotensin 1-converting enzyme (ACE) inhibition by LTPs could not be confirmed in plasma.

Herbal medicines as diuretics: a review of the scientific evidence.

There is increasing interest in the health and wellness benefits of herbs and botanicals. This is with good reason as they might offer a natural safeguard against the development of certain conditions and be a putative treatment for some diseases. One such area may be the lowering of blood pressure in those where it is elevated (i.e., hypertension). One class of clinical medicines used to lower blood pressure are known as diuretics and work by increasing the excretion of urine from the body as well as the amount of sodium in urine. There are a growing number of studies purporting diuretic effects with traditional medicines. The aim of this article was to review these studies and identify which extracts promote diuresis (which we assessed on terms of urine excreted and urinary sodium excretion) and also to identify the research needs in this area. We identified a number of species and genuses reporting diuretic effects. Of these, the most promising, at the present time, are the species Foeniculum vulgare, Fraxinus excelsior, Hibiscus sabdariffa, Petroselinum sativum and Spergularia purpurea, and species from the genuses Cucumis (Cucumis melo and Cucumis trigonus), Equisetum (Equisetum bogotense, Equisetum fluviatile, Equisetum giganteum, Equisetum hiemale var. affine and Equisetum myriochaetum), Lepidium (Lepidium latifolium and Lepidium sativum), Phyllanthus (Phyllanthus amarus, Phyllanthus corcovadensis and Phyllanthus sellowianus) and Sambucus (Sambucus mexicana and Sambucus nigra). However, there the number of studies is limited and we recommend that further studies be conducted to confirm reported effects. Such evidence is needed to provide scientific credence to the folklore use of traditional medicines and even be helpful in the development of future medicines, treatments and treatment guidelines.

Allergenicity of refined vegetable oils.

Several commercially important refined vegetable oils are derived from plants which are recognized as potent food allergens (e.g. peanut, soy). Full refining of oils results in the almost complete removal from oils of protein, which is responsible for allergic reactions. However, it is uncertain whether the minute amounts remaining could provoke allergic reactions in highly susceptible individuals. This has led to a vigorous debate about the safety of refined oils and specifically whether to label each oil individually because of the potential risk of allergenicity. Peanut oil has been the most thoroughly studied. It has been shown, in well-designed studies, that refined peanut oil can be safely consumed by the vast majority of peanut-allergic individuals, whereas unrefined oil can provoke reactions in some of the same individuals. However, some other studies report cases of allergic individuals reacting to oils, which are presumed to be refined. While it is likely that the discrepancy between these observations is due to differences in the processing of the oils, and possibly the protein content, this has not been formally demonstrated. Few data exist on the potential allergenicity of other edible vegetable oils; what data there are suggest that the major oils (soy, maize, sunflower, palm) do not provoke allergic reactions in susceptible individuals. Determining the content and immunoreactivity of the residual protein of refined oils is crucial to assessing the allergenic risk they present. Current methodology is inadequate and has not been validated for use with oils and aqueous extracts from oils. Little is known about the importance of different processing steps on allergenicity, although this information is crucial to risk assessment, particularly when considering process modifications. Available data suggest that the protein content of crude oils is of the order of 100-300 microg and that refining results in levels up to about 100-fold lower. The review concludes that peanut oil, and by extrapolation other edible vegetable oils, presents no risk of provoking allergic reactions in the overwhelming majority of susceptible people. However, there is a need to standardize and validate methodology for measuring the protein content and immunoreactivity of such so that they can be used to maintain process specifications. Thresholds of reactivity to allergens in man also need to be established in order to assess fully the risk from very small amounts.

House dust mite and cat allergen levels in domestic dwellings in Christchurch.

AIMS: To quantify the levels of Dermatophagoides pteronyssinus allergen (Der p I) and Felis domesticus allergen (Fel d I) in domestic dwellings in Christchurch and to assess possible relationships with housing characteristics. METHODS: Domestic dwellings (n = 93) were randomly selected and housing characteristics documented during the summer of 1994/95. Dust samples were obtained from the floor of the living room (LR) and bedroom (BR) and from the bed by standard vacuuming methods. The predominant mite species were determined and D pteronyssinus and F domesticus levels quantified. RESULTS: D pteronyssinus was the predominant (95%) species. D pteronyssinus allergen levels [geomean (95% confidence intervals) were 3.5(2.5-4.8) micrograms/g in LR, 10.1(7.5-13.7) micrograms/g in BR and 5.7(4.3-7.6) micrograms/g in the bed. F domesticus allergen levels were significantly higher (p < 0.001) in houses with cats than without cats [median (range) 93.2 (3.3-1227.2) micrograms/g and 2.9 (0.4-214.8) micrograms/g respectively]. Higher LR D pteronyssinus allergen levels were found in houses classified as having high indoor humidity and in houses situated in geographically damp locations. CONCLUSIONS: Domestic D pteronyssinus and F domesticus allergen levels in Christchurch are comparable with those found in other climatically similar locations. D pteronyssinus allergen levels are associated with both indoor and outdoor humidity factors.

Cardioprotection by ischemic and nonischemic myocardial stress and ischemia in remote organs. Implications for the concept of ischemic preconditioning.

Ischemic preconditioning studies employ one or more brief total coronary artery occlusions separated by complete reperfusion to limit infarct size during a subsequent prolonged coronary artery occlusion. We now present evidence that in anesthetized pigs a partial coronary artery occlusion without intervening reperfusion between the partial and prolonged total occlusions can also precondition the myocardium provided that the reduction in coronary blood flow is sufficiently severe. Thus infarct size was reduced after a 60 min total coronary artery occlusion when the total occlusion was preceded by a partial coronary occlusion that reduced coronary blood flow by 70% but not when the flow reduction was only 30%. In this two-stage coronary occlusion model the degree of protection appears greater in the epicardial than in the endocardial half. In view of evidence that brief occlusions of a coronary artery also protect myocardium outside its perfusion territory, we subsequently investigated whether ischemia in remote organs can protect myocardium. Because of reports that development of infarct size may be temperature dependent, we also investigated whether the cardioprotection by remote organ ischemia was temperature dependent. In anesthetized rats a 15 min coronary artery occlusion was more effective in reducing infarct size produced by a subsequent 60 min total coronary artery occlusion when the experiments were performed at a body core temperature of 30-31 degrees C than at 36-37 degrees C, while infarct size of animals which were subjected to only the 60 min total coronary artery occlusion was the same for the two body core temperatures. In rats with a body core temperature of 36-37 degrees C a 15 min mesenteric artery occlusion, but not a 15 min renal artery occlusion, reduced infarct size produced by a subsequent 60 min coronary artery occlusion. When the experiments were performed at 30-31 degrees C both the mesenteric and renal artery occlusions were protective. These observations indicate the local myocardial ischemia is not required to protect the myocardium during a prolonged coronary occlusion. We further investigated whether myocardium could also be protected by a cardiac stimulus which does not produce ischemia at all. For this purpose we electrically paced the left ventricle of anesthetized pigs to produce heart rates of 200 bpm (which did not lead to ischemia as assessed by a number of functional and biochemical variables) and found that 30 min of ventricular pacing reduced myocardial infarct size produced by a subsequent 60 min coronary artery occlusion. The protection by ventricular pacing involved activation of K+ATP channels as pretreatment with glibenclamide abolished the protection by ventricular pacing. We conclude that a number of distinctly different stimuli can protect the myocardium suggesting that ischemic myocardial preconditioning could be just one feature of a more general protection phenomenon.

Rapid ventricular pacing produces myocardial protection by nonischemic activation of KATP+ channels.

BACKGROUND: Rapid ventricular pacing reduces the incidence of ventricular arrhythmias during a subsequent sustained period of ischemia and reperfusion. We investigated whether rapid ventricular pacing also limits myocardial infarction and determined the role of KATP+ channels in the protection afforded by ventricular pacing. METHODS AND RESULTS: Myocardial infarction was produced by a 60-minute coronary artery occlusion in open chest pigs. Infarct size of pigs subjected to 10 minutes of ventricular pacing at 200 beats per minute followed by 15 minutes of normal sinus rhythm before the occlusion (79 +/- 3% of the area at risk, mean +/- SEM) was not different from control infarct size (84 +/- 2%). Thirty-minute pacing followed by 15-minute sinus rhythm resulted in modest reductions in infarct size (71 +/- 2%, P<.05 versus control). Thirty minutes of pacing immediately preceding the occlusion without intervening sinus rhythm resulted in considerable limitation of infarct size (63 +/- 4%, P<.05), which was abolished by pretreatment with the KATP+ channel blocker glibenclamide (78 +/- 4%, P=NS). KATP+ channel activation did not appear to involve ischemia: (1) myocardial endocardial/epicardial blood flow ratio was 1.07 +/- 0.08, (2) phosphocreatine and ATP levels and arterial-coronary venous differences in pH and PCO2 were unchanged, (3) end-systolic segment length did not increase and postsystolic shortening was not observed during pacing, and (4) systolic shortening recovered immediately to baseline levels and coronary reactive hyperemia was absent after cessation of pacing. Administration of glibenclamide after 30 minutes of pacing at the onset of 15 minutes of normal sinus rhythm did not attenuate the protection (73 +/- 3%, P<.05 versus control), suggesting the KATP+ channels did not contribute to the moderate degree of protection that was still present 15 minutes after cessation of pacing. CONCLUSIONS: Rapid ventricular pacing protects the myocardium against infarction via nonischemic KATP+ channel activation. Continued activation of KATP+ channels does not appear mandatory for the protection that is still present 15 minutes after cessation of pacing.

Endocardial and epicardial infarct size after preconditioning by a partial coronary artery occlusion without intervening reperfusion. Importance of the degree and duration of flow reduction.

OBJECTIVE: Recently, we reported that a partial coronary artery occlusion immediately preceding a sustained coronary artery occlusion limited infarct size. We now investigated whether the protection by partial coronary artery occlusions (i) depends on the severity and(or) duration of the flow reduction and (ii) varies in the different myocardial layers. METHODS: In 71 open-chest pigs (eight groups) left ventricular area at risk (AR) and infarct area (IA) were determined for the endocardial (IAendo and ARendo) and epicardial halves (IAepi and ARepi). RESULTS: In control animals (60 min total coronary artery occlusion (TCO) followed by 120 min reperfusion (Rep)) there were highly linear relations between IA and AR in the endocardium (r = 0.98, P < 0.01) and epicardium (r = 0.97, P < 0.01), which could be described by IAendo = 1.01 ARendo - 4.5 and by IAepi = 0.88ARepi - 3.6, respectively. In animals that underwent a 10 min TCO + 15 min Rep prior to the 60 min TCO + 120 min Rep, IA in both myocardial layers were again highly linearly related with AR, with less steep slopes for both the endocardium (0.63) and epicardium (0.57) (both P < 0.01). Two groups of pigs were subjected to either a 30 or 90 min 70% reduction in coronary blood flow (FR) immediately preceding the 60 min TCO + 120 min Rep, without intervening reperfusion. A 30 min 70% FR decreased IA to the same degree in the endo- and epicardial half. A 90 min 70% FR resulted in protection in the epicardium (P < 0.01) but not in the endocardium, most likely because 90 min 70% FR without 60 min TCO already caused infarction which was more severe in the endo- than in the epicardium (P < 0.01). Endocardial and epicardial IA after either a 30 or 90 min 30% FR prior to the 60 min TCO was not different from that in the control group, indicating that this mild flow reduction failed to limit irreversible damage. CONCLUSIONS: Thirty or ninety min of severe (70%) but not mild (30%) coronary flow reductions protected against myocardial infarction. The protection by a 70% FR was influenced by the duration of FR as a 30 min 70% FR similarly decreased IA in the endocardial and epicardial halves, while 90 min 70% FR preferentially limited IA in the epicardial half. These findings suggest that perfusion abnormalities immediately preceding an infarction could be an important source of infarct size variability in patients.

Ischaemic preconditioning by partial occlusion without intermittent reperfusion.

OBJECTIVE: The aim was to investigate whether ischaemic preconditioning can be obtained by a partial coronary artery occlusion without intermittent reperfusion. METHODS: In seven anaesthetised open chest pigs, the flow in the proximal left anterior descending coronary artery was reduced to 30% of baseline during 30 min before the vessel was occluded completely for 60 min (60 min total coronary occlusion, TCO). After 2 h of reperfusion, the area at risk (AR) and infarct size (IS) were determined using standard procedures. Infarct sizes were compared to those observed in control animals (n = 12), which were subjected to 60 min TCO and 2 h reperfusion, and to infarct sizes determined in animals preconditioned by 10 min TCO with either 15 min (n = 10) or 60 min (n = 5) of reperfusion before the 60 min TCO and 2 h reperfusion. In the last three groups of animals, area at risk was varied by occluding the coronary artery or its branches at different sites. RESULTS: In the control animals infarct size was linearly related (r = 0.99, p < 0.001) to the area at risk with a positive intercept on the AR axis: IS/LVmass (x100%) = 0.88 AR/LVmass (x100%)-3.6. At comparable areas at risk, the infarct size of the animals preconditioned with a 10 min TCO was less than for the control animals. For the animals preconditioned with 10 min TCO and 15 min reperfusion, the relationship between infarct size and area at risk was again linear (r = 0.88) and also had a positive intercept on the AR axis: IS/LVmass (x100%) = 0.68 AR/LVmass (x100%)-4.8. All animals with the flow reduction to 30% of baseline immediately preceding the 60 min TCO had infarct sizes smaller (p < 0.05) than predicted from the regression equation for the control animals, but the infarct size limitation could not be simply related to variables such as changes in regional systolic and postsystolic segment length shortening, ATP, or ADP during the partial occlusion period. CONCLUSIONS: Myocardium can be preconditioned with a flow reduction to 30% of baseline for 30 min without intermittent reperfusion (two stage Harris model). The positive intercept on the AR axis of the IS-AR relationship warrants caution of the use of IS/AR as an index for infarct size limitation.

Intracoronary trimetazidine does not improve recovery of regional function in a porcine model of repeated ischemia.

We evaluated the effect of trimetazidine (TMZ) on recovery of regional cardiac function in anesthetized open-chest pigs, subjected to fifteen 2-minute occlusions of the left anterior descending coronary artery, separated by 2 minutes of reperfusion and a 120-minute recovery period. Regional myocardial function was evaluated by sonomicrometry-derived segment lengthening and the area enclosed by the left ventricular pressure-segment length loop (external work, EW) in animals, which received either an intracoronary infusion of TMZ (33 micrograms/kg/min, n = 6) or saline (1 ml/min, n = 7), starting 15 minutes before the first occlusion and ending 2 minutes after the 15th occlusion. In addition, myocardial malondialdehyde production to evaluate oxygen free radical production, oxygen consumption, and the ATP, ADP, and AMP content, as well as the energy charge, were determined at regular time intervals. In control pigs the sequences of occlusion-reperfusion did not affect systemic hemodynamics, except for the LVdP/dtmax, which decreased by 11% during the interventions and did not recover during the following reperfusion period of 2 hours (78% of baseline, p < 0.05). Systolic segment length shortening and EW were increased at the end of the first occlusion-reperfusion cycle, decreased gradually during the remainder of the occlusion-reperfusion periods, and did not improve during the recovery period. Energy charge and myocardial blood flow were not impaired, but oxygen consumption was decreased during the recovery period. The malondialdehyde data did not provide evidence for production of oxygen free radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

Breakdown of 3,4-dihydroxybenzylamine and dopamine in plasma of various animal species by semicarbazide-sensitive amine oxidase.

We report a rapid breakdown of dopamine and especially of 3,4-dihydroxybenzylamine, the frequently-used internal standard in catecholamine determinations, in plasma of many but not all animal species. Species investigated were cow, sheep, goat, pig, horse, rabbit, dog, guinea pig, mouse, chicken, rat and man. In some species 3,4-dihydroxybenzylamine nearly completely disappeared at 4 degrees C within 15 min after addition to the plasma. Added dopamine, but not norepinephrine and epinephrine, also rapidly disappeared at 4 degrees C. Disappearance rates were increased at higher temperatures, and at 20 degrees C also norepinephrine showed some breakdown. The breakdown is caused by a semicarbazide-sensitive amine oxidase in the plasma, and can be completely blocked by the addition of the inhibitor semicarbazide. Measurement of plasma catecholamine concentrations in animal species can thus lead to erroneous results, especially when 3,4-dihydroxybenzylamine is used as an internal standard. Only when blood is collected in tubes containing an inhibitor of semicarbazide-sensitive amine oxidase like semicarbazide can reliable plasma catecholamine measurements be performed.

Metabolism of angiotensin I by different tissues in the intact animal.

To quantify regional conversion of angiotensin (ANG) I to ANG II and its degradation to peptides other than ANG II, monoiodinated 125I-labeled ANG I was given to anesthetized pigs by constant infusion into the left cardiac ventricle. At steady state, blood samples were taken from the aorta and various regional veins. Distribution volume of ANG I appeared to be 24% of body weight. After angiotensin-converting enzyme (ACE) inhibitor treatment, fractional ANG I metabolism (fraction of arterially delivered ANG I that was metabolized during a single passage of blood) was 10% in the lungs (conversion 4%), compared with 56% in the combined systemic vascular beds (conversion 1%). Fractional ANG I metabolism during ACE inhibition was 93% in the kidney; 50-70% in myocardium, skeletal muscle, head, and skin; 21% in the left cardiac cavity; and 14% in the right cardiac cavity. Without ACE inhibition, fractional ANG I metabolism was 29% in the lungs (conversion 25%); 49% in the combined systemic vascular beds (conversion 10%); 38% in the left cardiac cavity (conversion 11%); and 14% in the right cardiac cavity (conversion 0%). It may thus be concluded that 1) extrapulmonary vascular beds make an important contribution to the conversion of circulating ANG I and 2) there is rapid extrapulmonary ANG I degradation that does not depend on ANG I-II conversion.

Production of angiotensins I and II at tissue sites in intact pigs.

To estimate the contribution of angiotensin (ANG) I and II production at tissue sites to the circulating levels, ANG I and II and their radiolabeled counterparts were measured in arterial and venous plasma across various vascular beds during constant infusion of 125I-ANG I into the left cardiac ventricle of anesthetized pigs. In the combined systemic vascular beds, ANG I production was closely correlated with plasma renin activity (PRA) and ANG II production was greater than in the lungs. In the lungs virtually no ANG I but 31% of ANG II in venous plasma was derived from de novo production, which could be fully accounted for by conversion of circulating ANG I. In myocardium, head, skin, skeletal muscle, and kidney, respectively, 40, 58, 55, 67, and 94% of venous ANG I, and 32, 49, 40, 59, and 85% of venous ANG II were derived from de novo production. In these extrapulmonary beds part of de novo produced ANG I and II appeared not to be generated, respectively, by PRA and by conversion of circulating ANG I. These results indicate that production of ANG I at tissue sites contributes to its circulating level and that some circulating ANG II may not be derived from circulating ANG I.

Catecholamines and regional hemodynamics during isovolemic hemodilution in anesthetized pigs.

The effects of stepwise isovolemic hemodilution on systemic and regional hemodynamics, oxygen flux, and circulating catecholamines were studied in six pigs anesthetized with midazolam and fentanyl. Reduction of the hematocrit from 28 to 9% resulted in doubling of the cardiac output, mainly due to an increase in stroke volume. Regional blood flows, measured using the radioactive microsphere technique, showed an increase in blood flow to all organs except liver (hepatic artery fraction) and adrenals, with a redistribution of cardiac output in favor of heart and brain (increase in blood flow 420 and 170%, respectively). Oxygen flux to most organs did not decrease until hematocrit decreased to 9%, while total body oxygen consumption was well maintained. Left ventricular oxygen consumption increased, but because left ventricular blood flow also increased, left ventricular extraction ratio did not increase. Circulating catecholamines did not play any role in these regulatory mechanisms.

Adverse hemodynamic effects and echocardiographic consequences of pericardial closure soon after sternotomy and pericardiotomy.

The acute hemodynamic and echocardiographic effects of pericardial closure on cardiac function were studied in 11 pigs during steady-state anesthesia and ventilation. Observations were made after sternotomy, both while the pericardium was open and after it had been closed, and then after closure of the chest, after the pericardium had been reopened by removing the pericardial suture through the chest wall. In five pigs, further observations were made when a suture was tightened to close the pericardium while the chest remained closed. Closure of the pericardium when the chest was open reduced cardiac output by 14% and mean stroke volume by 19% (both p less than 0.05). Systemic vascular resistance increased by 15% when the pericardium was closed while the chest was open (NS), and increased by 19% when it was closed while the chest was closed (p less than 0.05). Heart rate did not change significantly, and the systemic blood pressure was maintained (-8%, NS). All these effects were reversed by opening the pericardium. Intrathoracic epicardial echocardiographic monitoring of the left ventricle showed that its end-diastolic dimension increased (by 11%, p less than 0.05) when the pericardium was opened. After chest closure, paradoxical motion of the interventricular septum was consistently demonstrated only during ventilation, and it was not related to whether or not the pericardium was open. This study suggests that cardiac function may be impaired by pericardial closure after cardiac surgery because of some degree of constriction of the heart chambers, although acute circulatory responses compensate for the mild decrease in stroke volume. Monitoring of blood pressure alone cannot document the subtle circulatory changes induced by pericardial closure, and therefore it is not a reliable guide to decisions of whether to close the pericardium or leave it open in individual patients.

Effects of administration of L-propionylcarnitine during ischemia on the recovery of myocardial function in the anesthetised pig.

The effects of L-propionylcarnitine (50 mg/kg) were studied in open-chest anesthetized pigs in which the blood flow in the left anterior descending coronary artery was reduced to 20% of baseline. A group of 7 animals given L-propionylcarnitine after 30 minutes of ischemia was compared with a group of 8 animals treated only with saline. After 60 minutes of ischemia the myocardium was reperfused for 2 hours. In both groups, the reduction of coronary artery blood flow abolished contraction of the affected myocardium and caused similar decreases in mean arterial blood pressure, the maximal rate of rise in left ventricular pressure, cardiac output, and ATP level and energy charge of the affected zone. L-propionylcarnitine did not affect any of these changes. Two hours of reperfusion caused further deterioration of systemic hemodynamics in both groups, although the decreases in cardiac output (P greater than 0.05) and mean arterial blood pressure (P less than 0.05) were smaller in the animals treated with L-propionylcarnitine. Left ventricular work, which decreased similarly in both groups during ischemia, deteriorated further in the saline treated group during reperfusion. This decrease was significantly attenuated by L-propionylcarnitine. Two hours of reperfusion resulted in only a partial return of blood flow to the reperfused ischemic myocardium, amounting to 53% of baseline in the saline-treated and to 72% of baseline in the L-propionylcarnitine-treated animals. The energy charge increased in both groups, but the increment tended to be less (P greater than 0.05) in the animals which had received L-propionylcarnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

The central and regional cardiovascular responses to intravenous and intracoronary administration of the phenyldihydropyridine elgodipine in anaesthetized pigs.

1. The central and regional cardiovascular responses to intravenous (0.3, 1.0, 3.0 and 10.0 micrograms kg-1 min-1) and intracoronary (0.3, 0.9, 3.0 and 4.5 micrograms kg-1 min-1) infusions of elgodipine, a phenyldihydropyridine, and its solvent were studied in anaesthetized pigs. 2. Elgodipine (i.v.) caused dose-dependent decreases in arterial blood pressure (up to 44%) and systemic vascular resistance (up to 48%), whereas heart rate, LV dP/dtmax, left ventricular filling pressure, cardiac output and segment length shortening did not change. The absence of a negative inotropic effect with the employed doses was confirmed by the intracoronary infusions; with the lowest dose (0.3 micrograms kg-1 min-1) both LV dP/dtmax and segment length shortening decreased by less than 10%. With 0.9 micrograms kg-1 min-1 (intracoronary) the negative inotropic properties of the drug became apparent as LV dP/dtmax and segment length shortening decreased by 20% and 33%, respectively, whereas heart rate and left ventricular filling pressure were not affected. 3. Transmural myocardial blood flow did not change during intravenous infusion of elgodipine, as vasodilatation, more pronounced in the subepicardial than in the subendocardial layers, compensated for the decrease in arterial perfusion pressure. The intracoronary infusions revealed that the decrease in normalized subendocardial/subepicardial blood flow ratio was not secondary to the fall in arterial blood pressure. 4. Myocardial oxygen consumption decreased during both the i.v. and the intracoronary administration of elgodipine. With the i.v. administration the decrease was secondary to the hypotensive action of the drug, whereas with the intracoronary administration the negative inotropic properties played the dominant role. 5. Elgodipine (i.v.), although not affecting total cardiac output, caused a redistribution in favour of the nutritional blood flow at the expense of the arteriovenous anastomotic (AVA) blood flow. Up to an infusion rate of 3.0upg kg - I min- 1 the decrease in AVA-flow was due to a fall in arterial blood pressure, but at the highest infusion rate both the decrease in arterial perfusion pressure and an increase in their resistance contributed to a further decrease in AVA blood flow. 6. The skeletal muscles benefited most from the elgodipine(i.v.)-induced increase in nutritional blood flow, but vasodilatation was not uniform for all muscle groups. Up to an infusion rate of 3 yg kg - ' min- 1 the vasodilatation in the renal vascular bed was more pronounced in the inner than in the outer cortex, but, at 0 pyg kg-1 min-, vascular resistances of both cortical layers returned to baseline values. In all regions of the brain, blood flow was maintained until the highest infusion rate was given. With 10 yg kg- I min - ' only flow to the vital parts of the brain (diencephalon and brain stem) was maintained. Blood flows to the skin and various abdominal organs were well maintained up to 3 pg kg'- min - 1 but, at the highest dose, a decrease was observed in blood flow to the adrenals and spleen. Vascular resistances of all these organs and tissues decreased dose-dependently. 7. The potent systemic and coronary vasodilator actions of elgodipine during i.v. administration, which were not accompanied by negative inotropic and positive chronotropic properties or decreases in the perfusion of vital organs, warrant further study as this compound could be useful in the treatment of essential hypertension, myocardial ischaemia and, possibly, moderate chronic heart failure.

Differential effects of n-3 fatty acids on the regression of atherosclerosis in coronary arteries and the aorta of the pig.

Atherosclerosis was induced in 13 Yorkshire pigs (4 weeks; 7-10 kg) by endothelial balloon denudation of the aorta and left anterior descending coronary artery and a diet containing 2% (wt/wt) of cholesterol, 8% (wt/wt) of lard fat and 0.5% (wt/wt) of bile acids. After 8 months 7 animals (group I) were sacrificed to determine the extent to which atherosclerosis had developed. The other 6 animals (group R) received a diet (no cholesterol, 5% (wt/wt) of lard fat and 5% (wt/wt) of fish oil) for 4 months. In I plasma cholesterol increased from 2.29 to 9.02 mmol l-1 after 8 months and in R it returned to 1.89 mmol l-1 after 12 months. Less marked changes occurred in plasma HDL cholesterol and triglycerides. ADP-induced platelet aggregation and the number of platelets remained constant in I whereas both parameters were reduced in R after 12 months. In the lesions of the abdominal aorta of I, cholesterol, cholesterol ester, phospholipid and triglyceride contents were 4.97, 2.08, 4.20 and 0.77 micrograms g-1 wet wt, respectively, whereas in R these values (3.02, 0.47, 2.70 and 0.44 micrograms g-1 wet wt, respectively), were close to the values measured in non-abraded vessel wall specimens. The Sudan IV-positive area of the aorta was 34 +/- 9% in I and 10 +/- 4% in R (P less than 0.05). Luminal encroachment of the denudated left anterior descending coronary artery was 11 +/- 3% in I and 13 +/- 3% in R (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)