Angelica Wackenfors

Effects of vacuum‐assisted closure therapy on inguinal wound edge microvascular blood flow

Vacuum‐assisted closure (VAC) therapy has been shown to facilitate wound healing. Data on the mechanisms are scarce, although beneficial effects on blood flow and granulation tissue formation have been presented. In the current study, laser Doppler was used to measure microvascular blood flow to an inguinal wound in pigs during VAC therapy (− 50 to − 200 mmHg), including consideration of the different tissue types and the distance from the wound edge. VAC treatment induced an increase in microvascular blood flow a few centimeters from the wound edge. The increase in blood flow occurred closer to the wound edge in muscular as compared to subcutaneous tissue (1.5 cm and 3 cm, at − 75 mmHg). In the immediate proximity to the wound edge, blood flow was decreased. This hypoperfused zone was increased with decreasing pressure and was especially prominent in subcutaneous as compared to muscular tissue (0–1.9 cm vs. 0–1.0 cm, at − 100 mmHg). When VAC therapy was terminated, blood flow increased multifold, which may be due to reactive hyperemia. In conclusion, VAC therapy affects microvascular blood flow to the wound edge and may thereby promote wound healing. A low negative pressure during treatment may be beneficial, especially in soft tissue, to minimize possible ischemic effects. Intermittent VAC therapy may further increase blood flow.

Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and coronary arteries: relationship to clinical effect

Triptans are agonists at 5-HT1B and 5-HT1D (where 5-HT is 5-hydroxytryptamine; serotonin) receptors and cause vasoconstriction of isolated blood vessels. The aim of the present study was to determine vasoconstrictor potency (EC50) of triptans in human coronary and cerebral arteries and to examine whether there was any relationship with the maximal plasma concentrations (Cmax; nM) of the drugs achieved following oral administration of clinically relevant doses to man using values reported in the literature. We also examined the expression of 5-HT1B receptors in atherosclerotic and normal coronary arteries. The vasocontractile responses to sumatriptan, rizatriptan or eletriptan were characterized by in vitro pharmacology. The ratio of Cmax/EC50 was calculated. 5-HT1B and 5-HT1D receptors were visualized by immunohistochemical techniques in coronary arteries. Sumatriptan, rizatriptan and eletriptan were powerful vasoconstrictors in cerebral artery. The rank order of agonist potency was eletriptan=rizatriptan=sumatriptan. In the coronary artery, the triptans were weaker vasoconstrictors. The rank order of potency was similar. In cerebral artery the ratio of Cmax/EC50 was not significantly different from unity, indicating a relationship between these two parameters. In general for the coronary artery, the ratios were significantly less than unity, indicating no direct relationship. Immunohistochemistry showed expression of 5-HT1B receptors in the medial layer, but did not reveal any obvious difference in 5-HT1B receptor expression between normal and atherosclerotic coronary arteries. The results support the notion that triptans are selective vasoconstrictors of cerebral arteries over coronary arteries and that there is a relationship between vasoconstrictor potency in cerebral arteries and clinically relevant plasma levels.

The effect of vacuum-assisted closure therapy on the pig femoral artery vasomotor responses.

Vacuum‐assisted closure (VAC) is frequently used to treat wound infections. The aim of the present study was to evaluate the effect of VAC therapy on blood vessels. Vasodilatation and vasoconstriction were studied in isolated ring segments of the pig femoral artery after continuous VAC therapy of an inguinal wound for 12 hours. Vasoconstriction induced by endothelin‐1 (ET‐1), which is mainly an endothelin type A receptor agonist (Emax = 181 ± 2% of potassium), and the endothelin type B receptor agonist, sarafotoxin 6c (Emax = 30 ± 1%), were significantly increased after VAC therapy (ET‐1; 325 ± 3% and sarafotoxin 6c; 69 ± 1%). The norepinephrine‐, phenylephrine‐, and angiotensin II‐induced vasoconstrictions were not affected by VAC therapy. Acetylcholine induced an endothelium‐dependent dilatation that was enhanced after VAC therapy (Rmax = 38 ± 1% of norepinephrine‐preconstriction after sham and 47 ± 1% after VAC therapy, p < 0.05). The dilatory response was mediated by nitric oxide (Rmax = 39 ± 1%), prostaglandins (5 ± 1%) and endothelium‐derived hyperpolarizing factor (16 ± 1%), which were all significantly increased after VAC therapy. In conclusion, VAC therapy for 12  hours enhances an endothelin type A and type B receptor‐mediated vasoconstriction. This may be compensated for by a more efficacious endothelium‐dependent vasodilatation. No spontaneous bleeding, perforation, dissection, or other macroscopic change could be observed in the arteries exposed to VAC therapy.

One year follow-up of patients with refractory angina pectoris treated with enhanced external counterpulsation

BackgroundEnhanced external counterpulsation (EECP) is a non-invasive technique that has been shown to be effective in reducing both angina and myocardial ischemia in patients not responding to medical therapy and without revascularization alternatives. The aim of the present study was to assess the long-term outcome of EECP treatment at a Scandinavian centre, in relieving angina in patients with chronic refractory angina pectoris.Methods55 patients were treated with EECP. Canadian cardiovascular society (CCS) class, antianginal medication and adverse clinical events were collected prior to EECP, at the end of the treatment, and at six and 12 months after EECP treatment. Clinical signs and symptoms were recorded.ResultsEECP treatment significantly improved the CCS class in 79 ± 6% of the patients with chronic angina pectoris (p < 0.001). The reduction in CCS angina class was seen in patients with CCS class III and IV and persisted 12 months after EECP treatment. There was no significant relief in angina in patients with CCS class II prior to EECP treatment. 73 ± 7% of the patients with a reduction in CCS class after EECP treatment improved one CCS class, and 22 ± 7% of the patients improved two CCS classes. The improvement of two CCS classes could progress over a six months period and tended to be more prominent in patients with CCS class IV. In accordance with the reduction in CCS classes there was a significant decrease in the weekly nitroglycerin usage (p < 0.05).ConclusionThe results from the present study show that EECP is a safe treatment for highly symptomatic patients with refractory angina. The beneficial effects were sustained during a 12-months follow-up period.

Triptans induce vasoconstriction of human arteries and veins from the thoracic wall

A common side effect of migraine treatment with triptans is chest symptoms. The origin of these symptoms is not known. The aim of the present study was to examine the vasocontractile effect of triptans in human arteries and veins from the thoracic wall and in coronary artery bypass grafts. In vitro pharmacology experiments showed that the 5-hydroxytryptamine (5-HT) type 1B and 1D receptor agonists, eletriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan, induced vasoconstriction in the thoracic blood vessels from 38% to 57% of the patients. 5-carboxamidotryptamine (5-CT) and sumatriptan elicited a vasoconstriction that was antagonized by the 5-HT1B receptor antagonist SB224289, whereas the 5-HT1D receptor antagonist BRL115572 had no effect. 5-HT induced a contraction that was inhibited by the 5-HT2A receptor antagonist ketanserin. 5-HT2A, 5-HT1B, and 5-HT1D receptor mRNA levels were detected by real-time PCR in all blood vessels studied. In conclusion, triptans induce vasoconstriction in arteries and veins from the thoracic wall, most likely by activation of 5-HT1B receptors. This response could be observed in only 38% to 57% of the patients, which may provide an explanation for why a similar number of patients experience chest symptoms as a side effect of migraine treatment with triptans.

Increased ET(A) and ET(B) receptor contraction in the left internal mammary artery from patients with hypertension.

Patients with hypertension have an increased activity in the endothelin system and an increased vascular tone, which predisposes them to target organ damage. In the present study, in vitro pharmacology, real-time PCR and immunofluorescence techniques were used to show enhanced endothelin type A (ETA) and type B (ETB) receptor contraction and expression in the left internal mammary artery from patients with hypertension as compared to normotensive patients. These receptors may be important in the pathophysiology of hypertension.

Enhanced expression of contractile endothelin ET(B) receptors in rat coronary artery after organ culture.

Endothelin-1 is a potent vasoconstrictor mediating its effects via two receptor subtypes, the endothelin type A (ET(A)) preferentially situated on smooth muscle cells, mediating vasoconstriction and endothelin type B (ET(B)) mainly located on endothelial cells, mediating vasodilatation. In cardiovascular disease and in organ culture in vitro, endothelin ET(B) receptors are up-regulated on smooth muscle cells. The objectives of the present study were to characterise the endothelin receptor-induced vasoconstriction and quantify the endothelin receptor mRNA levels and immunoreactivity in fresh and cultured rat coronary arteries. We demonstrate that endothelin-1 induces strong and equal concentration-dependent contractions in fresh and cultured segments from the left anterior descending coronary artery. Sarafotoxin 6c, an endothelin ET(B) receptor agonist, had negligible effect in fresh arteries but produced significant vasoconstriction after organ culture. The endothelin ET(B) receptor mRNA level and the receptor protein immunoreactivity were increased, whereas the level of endothelin ET(A) receptor mRNA was down-regulated but not its receptor protein immunoreactivity after organ culture. Pharmacological inhibition of endothelium-derived dilatory mediators did not influence endothelin ET(A) or ET(B) receptor-mediated vasoconstriction in fresh segments. In cultured arteries, inhibition of endothelial vasodilators potentiated the effect of sarafotoxin 6c. In conclusion, endothelin ET(B) receptor stimulation in cultured coronary arteries elicits vasoconstriction. This is likely not related to endothelial dysfunction with putative loss of its vasodilator components, but rather explained by the up-regulation of contractile endothelin ET(B) receptors on smooth muscle cells.

Endothelin receptors in endothelium-denuded human coronary artery bypass grafts and coronary arteries.

BACKGROUND Coronary artery bypass graft (CABG) surgery is hampered by deleterious vasospasm in the vessel wall, especially in vein grafts. Endothelin (ET) is a strong vasoconstrictor that can be observed in increasing concentrations during CABG surgery. METHODS Endothelin-induced vasoconstriction was evaluated in isolated, endothelium-denuded vessel segments of the human saphenous vein (SV), left internal mammary artery (LIMA), and coronary arteries. The ET(A) and ET(B) receptor mRNA levels were quantified by real-time polymerase chain reaction (PCR) analysis. RESULTS The ET(A) and ET(B) receptor mRNA levels were significantly higher in the SV than in the LIMA and the coronary arteries. ET-1 induced a more efficacious contraction in the SV and LIMA as compared with in the coronary arteries. The ET(B) receptor agonist, Sarafotoxin 6c (S6c) stimulated constriction of the LIMA and SV, while inactive in the coronary arteries. The concentration-response curve for S6c was biphasic, suggesting activation of ET(A) receptors at high concentrations as this response could be inhibited by FR139317 (10 micromol/L), and ET(B) at low concentrations as this response could be inhibited by BQ788 (0.1 micromol/L). CONCLUSIONS Endothelin-induced vasoconstriction is mediated by ET(A) receptors alone in coronary arteries, while a combination of ET(A) and ET(B) receptors are of importance in SV and LIMA. Expression of contractile ET(B) receptors may be a pharmacologic disadvantage that contributes to the vasospasm during CABG surgery. The lower levels of ET(A) and ET(B) receptor mRNA in the LIMA and coronary arteries as compared with in the SV may provide one explanation for the better long- and short-term patency of LIMA as compared with SV grafts.

Vacuum-assisted closure of the sternotomy wound: respiratory mechanics and ventilation.

Background: Numerous authors have reported promising results with the use of vacuum-assisted closure therapy in poststernotomy mediastinitis. The negative pressure applied to the anterior mediastinum substantially exceeds the normal negative pressure in the pleural cavities, and interaction with respiratory physiology cannot be excluded. The aim of the present study was to evaluate whether the application of six clinically relevant negative pressures between –50 mmHg and –175 mmHg to the sternotomy wound affects respiratory parameters in a porcine model. Methods: A midline sternotomy was performed in six mechanically ventilated pigs weighing 70 ± 3 kg. Vacuum-assisted closure therapy was applied with continuous negative pressure in a randomized order to the sternotomy wound. The following respiratory parameters were monitored by a carbon dioxide–based noninvasive monitoring system connected to the ventilator: carbon dioxide elimination, peak inspiratory pressure, peak expiratory flow, alveolar minute volume, alveolar tidal volume, expired tidal volume, static compliance, and airway resistance. Results: All pigs survived the treatment, and there was no significant change in the respiratory parameters investigated at any of the six negative pressures applied. A tendency toward increased airway resistance was noted when –175 mmHg was applied, although this change was not significant. Conclusions: The application of negative pressure therapy in the treatment of deep poststernotomy infections is a novel modality gaining increased attention. In this study, no impairment in respiratory mechanics, ventilation, or oxygenation was detected when comparing applied pressures ranging from –50 mmHg to –175 mmHg in the sternotomy wound.

Comparison of the antagonistic effects of different angiotensin II receptor blockers in human coronary arteries

Angiotensin II (Ang II) is a potent vasoconstrictor and a deleterious factor in cardiovascular pathophysiology. Ang II receptor blockers (ARBs) have recently been introduced into clinical practice for treatment of hypertension and congestive heart failure.