Perfusion of the human finger during cold-induced vasodilatation. (33/9283)

We have investigated the effect of severe local cooling on the vasomotor activity of the arteriovenous anastomoses (AVAs) and other finger vessels. The right third finger was subjected to local cooling (3 degrees C) for 30-45 min in 21 healthy, thermoneutral subjects. Blood velocity in the third finger arteries of both hands was simultaneously recorded using ultrasound Doppler, and skin temperature and laser-Doppler flux from the pulp of the cooled finger were also recorded. The results demonstrate that the initial cold-induced vasoconstriction during severe local cooling involves constriction of the AVAs as well as the two main arteries supplying this finger. During cold-induced vasodilatation (CIVD), the maximum velocity values were not significantly different from those before cooling. Furthermore, the velocity fluctuations in the cooled finger were in most subjects found to be synchronous with the velocity fluctuations in the control finger. This indicates that the large blood flow to the finger and the high skin temperature during CIVD are caused by relaxation of the smooth muscle cells of the AVAs.  (+info)

Responses of sympathetic outflow to skin during caloric stimulation in humans. (34/9283)

We previously showed that caloric vestibular stimulation elicits increases in sympathetic outflow to muscle (MSNA) in humans. The present study was conducted to determine the effect of this stimulation on sympathetic outflow to skin (SSNA). The SSNA in the tibial and peroneal nerves and nystagmus was recorded in nine subjects when the external meatus was irrigated with 50 ml of cold (10 degrees C) or warm (44 degrees C) water. During nystagmus, the SSNA in tibial and peroneal nerves decreased to 50 +/- 4% (with baseline value set as 100%) and 61 +/- 4%, respectively. The degree of SSNA suppression in both nerves was proportional to the maximum slow-phase velocity of nystagmus. After nystagmus, the SSNA increased to 166 +/- 7 and 168 +/- 6%, respectively, and the degree of motion sickness symptoms was correlated with this SSNA increase. These results suggest that the SSNA response differs from the MSNA response during caloric vestibular stimulation and that the SSNA response elicited in the initial period of caloric vestibular stimulation is different from that observed during the period of motion sickness symptoms.  (+info)

Myocardial temperature reduction attenuates necrosis after prolonged ischemia in rabbits. (35/9283)

OBJECTIVE: Previously we observed that a large reduction in infarct size was attained by cooling the risk region of the heart, either before or early after the onset of a 30-min coronary artery occlusion. While this is a standard duration of ischemia used in the rabbit model of infarction, it may not reflect the situation of patients who are reperfused late. The effects of regional hypothermia with a longer duration of ischemia, and when the intervention is applied later, are unknown. This study tests the hypothesis that a local reduction in cardiac temperature protects myocardium during prolonged ischemia (2 h) even if begun well after coronary artery occlusion. METHODS: Anesthetized rabbits received 2 h of coronary artery occlusion and 3 h of reperfusion. Rabbits were randomly assigned to a treated group: topical myocardial cooling starting 30 min after coronary occlusion (n = 14), or control group, no intervention (n = 12). Myocardial temperature in the risk zone, hemodynamics and regional myocardial blood flow were measured. RESULTS: Ischemic zone temperature was similar in both groups at 30 min post occlusion, but the cooling maneuver produced a reduction in temperature in the risk region of the treated group such that myocardial temperature was reduced an average of 10 degrees C between 30 and 60 min of coronary artery occlusion. Myocardial temperature in the control group remained within 0.3 degree C of baseline during coronary artery occlusion and into reperfusion. Core temperatures were similar in both groups. Hemodynamic parameters and collateral blood flow during occlusion were also equivalent in both groups. After 120 min of coronary occlusion, necrosis in the control group comprised 72 +/- 3% of the ischemic risk region. However, in cooled hearts, infarct size, expressed as a fraction of the risk region was significantly lower. Infarct size in this group averaged 59 +/- 3% of the risk region (p < 0.004 vs. controls), and thus cooling resulted in a salvage of approximately 18% of the risk region. CONCLUSION: These results show that reducing myocardial temperature protects ischemic myocardium during a long duration of ischemia even if initiated after coronary artery occlusion.  (+info)

Endothelial function is impaired in fit young adults of low birth weight. (36/9283)

OBJECTIVE: Non-insulin-dependent diabetes, hypertension and ischaemic heart disease, with insulin resistance, are associated with low birth weight (the 'Small Baby Syndrome'). Common to these adult clinical conditions is endothelial dysfunction. We tested the hypothesis that endothelial dysfunction could precede their development in those of low birth weight. METHODS: Endothelial function was measured by ultrasonic 'wall-tracking' of flow-related brachial artery dilatation in fit 19-20 year old subjects randomly selected (blind to the investigators throughout the study) from low (< 2.5 kg) and normal (3.0-3.8 kg) birth weight subjects in the 1975-7 cohort of the Cardiff Births Survey and with no known cause for endothelial dysfunction. RESULTS: Flow-related dilatation was impaired in low birth weight relative to normal birth weight subjects (median 0.04 mm [1.5%] [n = 22] cf. 0.11 mm [4.1%] [n = 17], p < 0.05; 0.04 mm [1.5%] [n = 15] cf. 0.12 mm [4.4%] [n = 12], p < 0.05 after exclusion of inadvertently included ever-smokers). CONCLUSION: The findings suggest that endothelial dysfunction is a consequence of foetal malnutrition, consistent with contributing to the clinical features of the 'Small Baby Syndrome' in later adult life.  (+info)

Blood flow influences vascular growth during tumour angiogenesis. (37/9283)

Many factors play a role in tumour angiogenesis. We observed growing tumour vessels in vivo to study the relationship between blood flow and vascular enlargement. Mammary adenocarcinoma was implanted into Fisher-344 rat with dorsal skin-fold transparent chambers. Vascular growth was observed and recorded on videotape through a microscope for 6 h. Vascular networks were photographed and traced every 30 min to identify changes over time. Tumour sections were stained with Masson's trichrome and anti-Factor VIII-related antigen. Tumour growth was rapid enough for differences to be seen each hour. Vessels with a high blood flow showed an increase in diameter within a few hours and new branches formed from these vessels. In contrast, vessels without an increase in blood flow showed no change in diameter. Vessels within the interstitium surrounding the tumour were lined by endothelium that was positive for anti-Factor VIII-related antigen staining. Vessels in the tumour had extremely rare endothelial cells detectable by Masson's trichrome or anti-Factor VIII-related antigen staining. In conclusion, increased blood flow may cause vascular enlargement and some primitive vessels seem to lack endothelium.  (+info)

Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. (38/9283)

Necrosis is a common feature of invasive carcinoma of the breast and is caused by chronic ischaemia leading to infarction. Although necrosis was previously assumed to be due to a generally poor blood supply in the tumour, in this study we show that it is present in tumours with focal areas of high vascular density situated away from the actual sites of necrosis. This may account, in part, for the previous observation that necrosis is linked to poor prognosis in this disease. Highly angiogenic tumours often display blood vessel shunting from one tumour area to another, which further exacerbates ischaemia and the formation of tumour necrosis. We have recently demonstrated that high focal microphage infiltration into breast tumours is significantly associated with increased tumour angiogenesis and poor prognosis and that the macrophages accumulate in poorly vascularized, hypoxic areas within breast tumours. In order to investigate the interactions of macrophages with chronic ischaemia (as reflected by the presence of necrosis) and angiogenesis in breast tumours, we quantified the levels of these three biological parameters in a series of 109 consecutive invasive breast carcinomas. We found that the degree of tumour necrosis was correlated with both microphage infiltration (Mann-Whitney U, P-value = 0.0009; chi-square, P-value = 0.01) and angiogenesis (Mann-Whitney U P-value = 0.0008, chi square P-value = 0.03). It was also observed that necrosis was a feature of tumours possessing an aggressive phenotype, i.e. high tumour grade (chi-square, P-value < 0.001), larger size (Mann-Whitney U, P-value = 0.003) and low oestrogen receptor status (Mann-Whitney U, P-value = 0.008; chi-square, P-value < 0.008). We suggest, therefore, that aggressive tumours rapidly outgrow their vascular supply in certain areas, leading to areas of prolonged hypoxia within the tumour and, subsequently, to necrosis. This, in turn, may attract macrophages into the tumour, which then contribute to the angiogenic process, giving rise to an association between high levels of angiogenesis and extensive necrosis.  (+info)

Enhancement of fluid filtration across tumor vessels: implication for delivery of macromolecules. (39/9283)

Cancer therapies using genes and other macromolecules might realize their full clinical potential if they could be delivered to tumor tissue in optimal quantities. Unfortunately, the compromised circulation within tumors poses a formidable resistance to adequate and uniform penetration of these agents. Previously, we have proposed elevated interstitial fluid pressure (IFP) as a major physiological barrier to delivery of macromolecules. Here we postulate that modulation of tumor microvascular pressure (MVP) and associated changes in IFP would enhance macromolecular delivery into a solid tumor. To test our hypothesis, we altered tumor MVP by either periodic injection or continuous infusion of angiotensin II (AII) and measured the resulting changes in IFP and uptake of macromolecules. We used the nicotinyl hydrazine derivative of human polyclonal IgG (HYNIC-IgG) as a nonspecific macromolecule and CC49 antibody as a specific macromolecule. We found that both chronic and periodic modulation of tumor MVP enhances transvascular fluid filtration, leading to a 40% increase in total uptake of the specific antibody within 4 hr of its administration. Conversely, neither continuous nor periodic infusion of AII induced any increase in uptake of nonspecific antibodies. Strategies to improve delivery of macromolecules and limitations of this approach are identified.  (+info)

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo. (40/9283)

Insulin-mediated changes in blood flow are associated with altered blood flow distribution and increased capillary recruitment in skeletal muscle. Studies in perfused rat hindlimb have shown that muscle metabolism can be regulated by vasoactive agents that control blood flow distribution within the hindlimb. In the present study, the effects of a vasoconstrictive agent that has no direct effect on skeletal muscle metabolism but that alters perfusion distribution in rat hindlimb was investigated in vivo to determine its effects on insulin-mediated vascular action and glucose uptake. We measured the effects of alpha-methylserotonin (alpha-met5HT) on mean arterial blood pressure, heart rate, femoral blood flow, hindlimb vascular resistance, and glucose uptake in control and euglycemic insulin-clamped (10 mU x min(-1) x kg(-1)) anesthetized rats. Blood flow distribution within the hindlimb muscles was assessed by measuring the metabolism of 1-methylxanthine (1-MX), an exogenously added substrate for capillary xanthine oxidase. Alpha-met5HT (20 microg x min(-1) x kg(-1)) infusion alone increased mean arterial blood pressure by 25% and increased hindlimb vascular resistance but caused no change in femoral blood flow. These changes were associated with decreased hindlimb 1-MX metabolism indicating less capillary flow. Insulin infusion caused decreased hindlimb vascular resistance that was associated with increased femoral blood flow and 1-MX metabolism. Treatment with alpha-met5HT infusion commenced before insulin infusion prevented the increase in femoral blood flow and inhibited the stimulation of 1-MX metabolism. Alpha-met5HT infusion had no effect on hindlimb glucose uptake but markedly inhibited the insulin stimulation of glucose uptake (P < 0.05) and was associated with decreased glucose infusion rates to maintain euglycemia (P < 0.05). A significant correlation (P < 0.05) was observed between 1-MX metabolism and hindlimb glucose uptake but not between femoral blood flow and glucose uptake. The results indicate that in vivo, certain types of vasoconstriction in muscle such as elicited by 5HT2 agonists, which prevent normal insulin recruitment of capillary flow, cause impaired muscle glucose uptake. Moreover, if vasoconstriction of this kind results from stress-induced increase in sympathetic outflow, then this may provide a clue as to the link between hypertension and insulin resistance that is often observed in humans.  (+info)