The interactions between temperature and activity levels in driving metabolic rate: theory, with empirical validation from contrasting ectotherms.

The rate of change in resting metabolic rate (RMR) as a result of a temperature increase of 10 °C is termed the temperature coefficient (Q10), which is often used to predict how an organism's total MR will change with temperature. However, this method neglects a potentially key component of MR; changes in activity level (and thus activity MR; AMR) with temperature may significantly alter the relationship between MR and temperature. The present study seeks to describe how thermal effects on total MR estimated from RMR-temperature measurements can be misleading when the contribution of activity to total MR is neglected. A simple conceptual framework illustrates that since the relationship between activity levels and temperature can be different to the relationship between RMR and temperature, a consistent relationship between RMR and total MR cannot be assumed. Thus the thermal effect on total MR can be considerably different to the thermal effect on RMR. Simultaneously measured MR and activity from three ectotherm species with differing behavioural and physiological ecologies were used to empirically examine how changes in temperature drive changes in RMR, activity level, AMR and the Q10 of MR. These species exhibited varied activity- and MR-temperature relationships, underlining the difficulty in predicting thermal influences on activity levels and total MR. These data support a model showing that thermal effects on total MR will deviate from predictions based solely on RMR; this deviation will depend upon the difference in Q10 between AMR and RMR, and the relative contribution of AMR to total MR. To develop mechanistic, predictive models for species' metabolic responses to temperature changes, empirical information about the relationships between activity levels, MR and temperature, such as reported here, is required. This will supersede predictions based on RMR alone.

Discontinuous gas exchange exhibition is a heritable trait in speckled cockroaches Nauphoeta cinerea.

The regulation of insect respiratory gas exchange has long been an area of interest. In particular, the reason why insects from at least five orders exhibit patterns of gas exchange that include regular periods of spiracular closure has been the source of much controversy. Three adaptive hypotheses propose that these discontinuous gas-exchange cycles (DGCs) evolved to either limit water loss across respiratory surfaces, facilitate gas exchange in underground environments or to limit oxidative damage. It is possible that DGCs evolved independently multiple times and for different reasons, but for DGCs to be a plausible target for natural selection, they must be heritable and confer a fitness benefit. In a previous study of cockroaches Nauphoeta cinerea, we demonstrated that DGCs are repeatable and extend survival under food and water restriction. Here, we show for the first time that DGCs are heritable, suggesting that they are a plausible target for natural selection.

Outcome of endovascular intervention for infrainguinal vein graft stenosis.

Assisted graft patency rate following revision of a graft stenosis is far better than that following thrombectomy of an occluded graft. Graft revision by endovascular means has been proposed as a suitable alternative to more invasive surgery. This study reports our experience with endovascular treatment of vein graft stenosis. Between December 1992 and September 2000, percutaneous transluminal balloon angioplasty (PTA) was performed on 90 vein graft stenoses in 87 infrainguinal vein bypass grafts identified by routine graft duplex scan (peak systolic velocity, PSV > 300 cm/sec). All 90 stenoses treated by PTA were retrospectively analysed for stenosis-free patency rate (life-table analysis). Re-stenosis was defined by PSV exceeding 300 cm/sec at the same site of the vein graft where a stenosis was dilated. Ninety vein graft stenoses (72 primary stenoses and 18 recurrent stenoses) in 33 femoropopliteal (above knee), 30 femoropopliteal (below knee) and 24 femorotibial vein bypass grafts were treated by PTA. The timing of PTA ranged from one to 252 months (mean, 23.9 months) from the initial surgery. Cumulative stenosis-free patency rate after PTA was 55.8% at 6 months, 54.0% at one year and 45.0% at three years. Stenosis-free patency rate at six months was significantly lower for revision of recurrent stenosis (25.9%) than for primary stenosis (61.6%) (P = 0.01). The revision of duplex scan detected vein graft stenosis with endovascular intervention was associated with an acceptable stenosis-free patency rate. However, recurrent stenosis treated by PTA had a significantly inferior outcome. Direct surgical revision would be more appropriate for recurrent lesions.

Lipid levels and peripheral vascular disease in diabetic and non-diabetic subjects.

Non-insulin dependent diabetes (NIDDM) is associated with an increased risk of peripheral vascular disease (PVD), but within the diabetic population the relationship between lipid profile and PVD has not been clearly defined. In this study we examined the association of lipid parameters and in particular low density lipoprotein (LDL) particle size, with the presence of PVD in subjects with and without NIDDM. 41 NIDDM patients and 31 non-diabetic subjects with PVD in the absence of rest pain or ulceration, defined by ankle-brachial index measurements and duplex scanning, were compared with 41 NIDDM and 31 euglycemic control subjects of comparable age and sex, without PVD. In both groups those with PVD were found to have significantly elevated triglycerides (2.7 [2.2-3.3] versus 1.9 [1.6-2.2] mmol/l; P < 0.05 in the diabetic group and 2.0 [1.6-2.3] versus 1.4 [1.1-1.5] mmol/l; P < 0.05 in the non-diabetic group), decreased apolipoprotein A1 (124 +/- 3 versus 139 +/- 5 mg/dl; P < 0.01 in the diabetic group and 133 +/- 4 versus 147 +/- 4 mg/dl; P < 0.05 in the non-diabetic group) and decreased LDL particle size (25.4 +/- 0.1 versus 25.8 +/- 0.1 nm; P < 0.01 in the diabetic group and 26.0 +/- 0.1 versus 26.3 +/- 0.1 nm; P < 0.05 in the non diabetic group). In the non-diabetic group apolipoprotein[a] (365 [239-554] versus 184 [17-266] U/l; P < 0.01), total cholesterol (6.3 +/- 0.2 versus 5.6 +/- 0.2 mmol/l; P < 0.05), LDL cholesterol (4.1 +/- 0.2 versus 3.6 +/- 0.2 mmol/l; P < 0.05) and apolipoprotein B (146 +/- 8 versus 117 +/- 5 mg/dl; P < 0.05) were also found to be associated with PVD although these associations were not observed in the group with diabetes. In addition, 11 NIDDM subjects and 11 non-diabetic subjects with rest pain or ulceration were compared to the corresponding groups with uncomplicated PVD and had lipid profiles with significantly lower levels of total cholesterol and LDL cholesterol. We conclude that the dyslipidemic profile characterized by increased triglyceride level, decreased apolipoprotein A1 level and small dense LDL is associated with uncomplicated PVD in both NIDDM and non-diabetic subjects.

Clinical and vascular laboratory determinants for outcome after infrainguinal atherectomy.

Three surgeons performed 180 atherectomy procedures in 161 patients using the Transluminal Extraction Catheter in 144 and the Auth Rotablator in 36. The primary patency rate was 55% at 1 year and 46% at 2 years, and failure was caused by stenosis in 28 (15.6%) and occlusion in 61 (33.7%) limbs. Multivariate Cox regression analysis showed significantly better outcome if the indication was claudication, the lesion was short or there was associated stenting. Vascular laboratory surveillance was performed in 93 limbs in 83 patients. Cox regression analysis in this subgroup also showed a significant relationship between outcome and the maximum peak systolic velocity from a duplex scan at the last study performed. Receiver operating characteristics curves showed that a raised maximum peak systolic velocity best predicted late failure (sensitivity 84%, specificity 66% for > 200 cm/s; sensitivity 72%, specificity 84% for > 250 cm/s); the velocity ratio at the stenosis to that in the segment above or the resting ankle/brachial pressure index were less predictive. For 50 procedures studied in the vascular laboratory which remained successful to the end of the study, maximum peak systolic velocities were > 250 cm/s from the first postoperative study, suggesting residual stenosis in 6%, or increased to become > 250 cm/s by the last study, suggesting recurrent stenoses in 12%. For 43 procedures which were studied and later failed, velocities were > 250 cm/s from the first test in 26% or increased to > 250 cm/s by the last test before failure in 40%. Vascular laboratory surveillance helps to predict outcome after atherectomy. Failure may be a result of residual disease from the time of the procedure or from restenosis. The apparent high incidence of clinically manifest or developing stenoses raises doubts as to the benefit of atherectomy over balloon dilatation alone.

Duplex ultrasonography scanning for chronic venous disease: patterns of venous reflux.

PURPOSE: Patterns of flow in superficial and deep veins and outward flow in medial calf perforators were studied by duplex ultrasonography scanning in 1653 lower limbs in 1114 consecutive patients. This study compares results in 776 limbs with primary uncomplicated varicose veins with those in 166 limbs with the complications of lipodermatosclerosis or past venous ulceration. METHODS: Duplex scanning determined whether superficial and deep veins were occluded or showed reflux and whether outward flow occurred in medial calf perforators with calf muscle contraction. RESULTS: Two proximal deep veins were occluded. When limbs with primary uncomplicated varicose veins, lipodermatosclerosis, or past ulceration were compared, superficial reflux alone was seen in 55%, 39%, and 38%, deep reflux alone was seen in 2%, 7%, and 8%, and combined superficial and deep reflux was seen in 18%, 34%, and 48%, respectively. Superficial reflux affected the long saphenous system alone in 58%, 57%, and 40%, the short saphenous system alone in 18%, 18%, and 26%, and both the long and short saphenous systems in 24%, 25%, and 34%, respectively. Limbs with ulceration more frequently showed superficial reflux (p < 0.05), and all limbs with complications more frequently showed short saphenous reflux (p < 0.05) and deep reflux (p < 0.01) specifically in the posterior tibial veins (p < 0.01). Outward flow was seen in medial calf perforators in 57%, 67%, and 66%, respectively; it occurred more frequently in all limbs with complications (p < 0.05). Isolated outward flow in perforators without superficial or deep reflux was seen in 10%, 10%, and 2%, respectively. CONCLUSIONS: Most limbs with complications had superficial reflux either alone or combined with deep reflux, and few had deep reflux alone. Reflux was more frequent in posterior tibial veins for limbs with complications compared with those with uncomplicated primary varicose veins. Outward flow in perforators was common in limbs with complications and with uncomplicated primary varicose veins, but isolated outward flow in perforators was uncommon. Treatment directed to the superficial veins alone may be sufficient for most patients with complications.

Improvement in arterial stiffness during hypolipidaemic therapy is offset by weight gain.

Fourteen patients with familial hypercholesterolaemia were managed with dietary advice and simvastatin for 12 months. Either nicotinic acid or cholestyramine resin was added to the regimen if serum cholesterol was not less than 5.5 mmol/l within 18 weeks. After dietary advice but before commencing pharmacotherapy for hyperlipidaemia, arterial stiffness was measured in the common carotid and common femoral arteries. These studies were repeated after 12 months on pharmacotherapy. The primary objective of this study was to determine whether arterial stiffness could be altered with total cholesterol and low density lipoprotein (LDL) cholesterol lowering. Over the 12 month interval, serum total cholesterol, LDL cholesterol and triglycerides fell significantly, whereas high density lipoprotein (HDL) cholesterol and body mass index (BMI) rose significantly. Mean supine blood pressure did not change significantly. Arterial stiffness in the common carotid artery decreased from 1.04 +/- 0.21 x 10(5) N/m2 to 0.63 +/- 0.06 x 10(5) N/m2 (T = -2.67, P < 0.01) over the interval. Stiffness of the common femoral artery decreased from 2.10 +/- 0.57 x 10(5) N/m2 to 0.83 +/- 0.15 x 10(5) N/m2 (T = -2.73, P < 0.01). The change in arterial stiffness was not directly related to changes in circulating lipids or supine blood pressure. Increase in BMI, however, correlated with change in arterial stiffness in the common femoral artery (Rs = 0.53, P < 0.05) but not in the common carotid artery. An increase in BMI was associated with a smaller decrease in common femoral arterial stiffness. Aggressive hypolipidaemic therapy was therefore associated with a favourable effect on arterial wall stiffness.(ABSTRACT TRUNCATED AT 250 WORDS)

Early post-operative ankle pressure indices help predict late patency rates after femoro-distal vein bypass grafting.

A prospective graft surveillance programme included 115 femorodistal autogenous vein bypass grafts that were patent when studied by measurements of ankle/brachial pressure indices (ABIs) at 3-5 weeks after operation. The grafts were followed for up to 3 years to determine whether early ABIs helped to predict subsequent failures, defined as graft thrombosis or graft or anastomotic stenosis causing diameter reduction greater than 75% treated by surgery or balloon dilatation. Receiving operating characteristics curves showed that resting ABIs predicted failure better than post-exercise ABIs or the differences between the two, and that an early resting ABI less than 0.85 was the optimal value to predict failure. Primary patency rates at 2 years were 88% for resting ABI greater than or equal to 0.85 and 36% for resting ABI less than 0.85 (p less than 0.0005). Most stenoses occurred in the grafts and not at anastomoses. Arteriographic grading of crural artery outflow was not significantly different for successful or failed grafts or for grafts with resting ABI greater than or equal to 0.85 or less than 0.85. The observation that late graft failure was 3-4 times more likely if the early post-operative ABI was low suggests that most graft failures result from faults relating to the operation.

Double-blind study of dilevalol and captopril, both in combination with hydrochlorothiazide, in patients with moderate to severe hypertension.

Sixty-one patients (41 men, 20 women) aged 29-73 years, with moderate to severe hypertension, were enrolled in a multicentre study to compare the efficacy, safety, and tolerability of dilevalol (D) and captopril (C). At the end of the baseline period, supine diastolic blood pressure (SuDBP) was 105-140 mm Hg on hydrochlorothiazide (HCTZ) 25 mg once daily and placebo t.i.d. Patients were randomly assigned to D + HCTZ (n = 29) or C + HCTZ (n = 32) and entered phase II titration of D (100-800 mg b.i.d.) or C (12.5 mg b.i.d. to 50 mg t.i.d.). If SuDBP was greater than 99 mm Hg, hydralazine was added (25 mg once daily to 50 mg b.i.d.). If SuDBP was less than or equal to 99 mm Hg, patients entered phase III, a 3-month maintenance period. Demographic profiles were not significantly different between the two groups. Baseline supine BP (mean +/- SEM) was similar in the two groups (D + HCTZ: 182 +/- 3/112 +/- 1; C + HCTZ: 179 +/- 4/113 +/- 1 mm Hg), as was baseline standing BP (D + HCTZ: 175 +/- 3/114 +/- 2; C +/- HCTZ: 173 +/- 4/113 +/- 1 mm Hg). At the end of phase II, there were no significant differences between treatments with respect to the changes in BP from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for coronary heart disease in a self-referred population compared with a general population.

Screening programmes for community coronary heart disease risk factors aim to identify persons who are at a high risk of the development of coronary heart disease by screening the population for the prevalence of smoking, obesity, high blood pressure and high blood cholesterol concentrations. The effectiveness of such screening programmes is dependent on a number of factors. The characteristics of individuals who attend such screening programmes voluntarily, and the prevalence of abnormal coronary heart disease risk factors that is detected, give a strong indication of the population reach and the potential benefits of the preventive strategy. In this study, persons who attended a self-referred risk-factor screening programme for coronary heart disease were compared with a random sample of the Australian urban population. A disproportionately high number of older persons and of women presented for the self-referred screening programme while smokers were underrepresented. In general, the risk-factor levels of those in the older age-groups who attended the screening programme were lower than were the corresponding measurements that were found in the random sample; the opposite was true for those in the younger age-groups. These results suggest that coronary heart disease risk-factor screening programmes in the community appeal more to those in the health-conscious older age-groups and to women. For heart disease prevention programmes to be more effective, it will be necessary to design screening programmes to attract more men, those in younger age-groups and smokers.

Comparison of felodipine extended release and conventional tablets in essential hypertension using ambulatory blood pressure monitoring.

Two formulations of felodipine, conventional and extended release (ER) tablets, were compared in a double-blind, crossover study of patients whose blood pressure was not being controlled using metoprolol 100 mg once daily. Nineteen patients with a supine diastolic blood pressure greater than or equal to 95 mmHg after 4 weeks of taking metoprolol and placebo were randomly assigned to felodipine conventional (5 mg twice a day) or ER (10 mg once daily) for 4 weeks. A 2-week washout period was then followed by 4 weeks of treatment with the alternative formulation. Metoprolol once daily was taken concomitantly throughout the study. Clinic blood pressure was measured at 0 h (i.e. 12 h after the last dose of conventional, and 24 h after the last ER felodipine dose), and then 2 and 5 h after the following dose had been taken. Ambulatory blood pressure and the heart rate were monitored over 24 h using an Accutracker (Suntech Medical Instruments, Raleigh, North Carolina, USA). During the final treatment, both felodipine formulations caused similar substantial falls in supine blood pressure compared with pressures prior to randomized treatment. The falls in clinic blood pressures (systolic/diastolic) were similar with the conventional and ER formulations at all time points, i.e. 0 h (21/13; 19/11 mmHg), 2 h (39/18; 36/18 mmHg) and 5 h (30/12; 35/11 mmHg) after the morning dose was taken. Both formulations also produced similar falls in blood pressures over 24 h and during the daytime (21/12; 20/12 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of cross sensitivity between captopril and enalapril.

Oral inhibitors of angiotensin converting enzyme (ACE) now have an established place in the treatment of hypertension and heart failure. Captopril, the first of these agents, was initially used in high doses and was associated with adverse effects including proteinuria, skin rash and taste disturbance. We report 11 patients who developed side effects during captopril therapy (proteinuria two, rash four, taste disturbance four and taste disturbance with rash one) who were subsequently treated with enalapril, a second generation angiotensin converting enzyme inhibitor. Proteinuria did not recur in either patient, skin rash resolved in all five cases and taste disturbance resolved in four of five during enalapril therapy. We conclude that the side effects of proteinuria, skin rash and taste disturbance are consequences of captopril idiosyncrasy rather than inhibition of the angiotensin converting enzyme. The reported incidence of these side effects with the current recommended dosage of captopril is low.

Differential renal function during angiotensin converting enzyme inhibition in renovascular hypertension.

Renal function was measured sequentially in 32 patients with proven renovascular hypertension who were treated with the oral angiotensin converting enzyme inhibitor captopril. Renal function was assessed by serial measurement of serum creatinine. Six patients showed acute rises in serum creatinine concentration compatible with acute renal failure. Acute renal failure was confined to those patients with stenosis to a solitary kidney (transplant or native, occurring in 3 of 8 patients) or bilateral renal artery stenosis (occurring in 3 of 13 patients). No rise in serum creatinine concentration was observed in 11 patients with unilateral renal artery stenosis during long-term angiotensin converting enzyme inhibitor therapy. Acute renal failure during angiotensin converting enzyme inhibitor therapy was not related to the degree of blood pressure fall or the plasma angiotensin II level. Eleven patients with renovascular hypertension were followed prospectively with estimation of renal function by 99mTc-diethylenetriaminepentaacetic acid (DTPA) clearance (determined by computer analysis of scintillation camera renography). In six patients with unilateral renal artery stenosis, total 99mTc-DTPA clearance and serum creatinine level remained constant following angiotensin converting enzyme inhibitor therapy, while in five patients with bilateral renal artery stenosis 99mTc-DTPA clearance fell from 40 +/- 9 to 27 +/- 5 ml/min (p less than 0.05). Split renal function studies revealed that 99mTc-DTPA clearance fell in most kidneys with stenosed arteries during angiotensin converting enzyme inhibition, including the stenosed kidney from patients with unilateral renal artery stenosis (16 stenosed kidneys studied; change in Tc-DTPA clearance, -7.5 +/- 2.7 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled trial of enalapril in congestive cardiac failure.

Twenty five patients with chronic congestive cardiac failure had enalapril (n = 13) or placebo (n = 12) added to their existing regimen of digoxin and frusemide in a randomised double blind trial. Four hours after the first 5 mg dose, the enalapril group showed significant falls in blood pressure, heart rate, and concentrations of plasma angiotensin II, angiotensin converting enzyme, and noradrenaline. During the 12 week trial heart failure became worse in one enalapril treated patient (8%) and in seven placebo treated patients (58%). There were no significant changes in cardiac ejection fraction or exercise duration in either group. Plasma noradrenaline response to graded exercise and maximum exercise rate-pressure product were significantly reduced after four and 12 weeks of active treatment but unchanged with placebo treatment. There was a sustained increase in plasma potassium and a slight rise in plasma creatinine in the enalapril group. Plasma concentrations of the active drug, enalaprilate, were dose related and log enalaprilate correlated significantly with percentage of plasma angiotensin converting enzyme activity (r = -0.66). Enalapril was well tolerated and produced no adverse effects. The drug appears to be superior to placebo and offers considerable promise for the treatment of this condition.

Bradykinin receptors in rat uterine smooth muscle: studies using radiolabeled ligand binding.

Direct binding of 125I-Tyr8-bradykinin to a microsomal fraction prepared from rat uterine smooth muscle, showed an apparent dissociation constant (KD) at 29 degrees C of 5.0 X 10(-10) M calculated from kinetic studies and 6.6 X 10(-10) M from Scatchard plot analysis. The binding of 125I-Tyr8-bradykinin was reversible and saturable, and demonstrated high specificity for Tyr8-bradykinin, bradykinin and Lys-bradykinin, but was not displaced by unrelated peptides angiotensin I, angiotensin II, Arg8-vasopressin and oxytocin. The binding sites were copurified by differential centrifugation and on a discontinuous sucrose density gradient with 5'-nucleotidase activity, a plasma membrane marker enzyme. Prolonged intravenous infusion of bradykinin (5 nmol/h for 2 days) induced a 20% decrease in the number of bradykinin binding sites without a change in the equilibrium dissociation constant. The present results demonstrate that receptors mediating the effect of bradykinin on rat uterine smooth muscle are situated on plasma membranes and the regulation of the receptors is in part under the control of endogenous bradykinin levels.

Hypotensive effect of captopril and decreased rat uterine bradykinin receptors.

To determine the role of local bradykinin at the level of the vascular smooth muscle receptors in the hypotensive effect of captopril, we assessed the effects of prolonged intravenous infusions for up to 7 days of bradykinin (0.1 microgram/min) and captopril (1.7 micrograms/min) on systolic blood pressure and uterine bradykinin receptors in normotensive rats. Bradykinin infusion was associated with a transient fall in systolic blood pressure at Day 1 (117.5 +/- 2.8 mmHg vs. 125.8 +/- 1.7, p less than 0.05) and returned to control levels by Day 3. Following captopril infusion there was a similar but more persistent fall in systolic blood pressure (115.3 +/- 2.4 mmHg vs. 125.8 +/- 1.7, p less than 0.01 at Day 1 and 111.0 +/- 2.4 mmHg vs. 125.0 +/- 1.9, p less than 0.001 at Day7). After 2 days of bradykinin infusion the number of bradykinin receptors was decreased (39.9 +/- 2.1 fmol/mg protein vs. 49. 9 +/- 2.4, p less than 0.01) and returned to controls at Day 7, while captopril infusion induced a prolonged decrease (42.3 +/- 1.8 fmol/mg protein vs. 49.9 +/- 2.4, p less than 0.05 at Day 2 and 38.8 +/- 2.4 fmol/mg protein vs. 44.5 +/- 1.3, p less than 0.05 at Day 7). Present results suggest that the increased vascular tissue level of bradykinin can contribute directly to the acute hypotensive effect of captopril. However, it may play only a minor role for the chronic hypotensive effect of captopril.

Influences of low sodium diets on vascular effects of bradykinin and on bradykinin receptors in the uterine smooth muscle in the rats.

A low sodium diet for 7 days in the rat induced an enhancement of the vascular effects of bradykinin, determined as the blood pressure response, by 56%. However, this enhancement reverted after 28 days of a low sodium diet. A sustained increase in the number of uterine smooth muscle bradykinin receptors during low sodium diets was observed, 1.3 times of the control on the 7th day and 1.7 times on the 28th day. No change in binding affinity was found in any of the studies. These results suggest that the vascular effects of bradykinin after low sodium diets may be regulated by homeostatic mechanisms via the change in the number of vascular smooth muscle bradykinin receptors at subcellular levels, and that the number of uterine smooth muscle bradykinin receptors may be affected by sodium status per se.