MMed thesis - Faculty of Health Sciences / The field of organ and tissue transplantation has necessitated an improved understanding of their associated pathophysiological pathways. Specific areas of interest involve the changes that follow ischaemia and derangement’s that accompany organ and tissue storage, reperfusion injury and the “no-reflow” phenomenon. Strategies have been devised to manipulate and modify these processes, improving tissue and organ survival and function. These have involved the use of preservation solutions. Although most research involves organ transplantation, these principles have been translated and applied to various tissues, surgical flaps and microvascular replantations. These studies have generally used the skin flap as their model with little knowledge regarding muscle flaps, the most vulnerable to the ischaemic process. This study targets the use of one such preservation system and uses skeletal muscle as its tissue model. The vascular anatomy of the rectus femoris muscle in the New Zealand white rabbit was studied anatomically and radiologically and thus described. The isolated rectus femoris muscle flap was harvested and perfused in-vitro with cooled, oxygenated University of Wisconsin solution (UWS) using a pulsatile renal perfusion pump. UWS was selected as it contains vital additives important in cryopreservation of organs. Monitoring of various physiological parameters was performed. The muscle was examined at 0, 4, 8, 12, 18 and 24 hours of extra-corporeal perfusion using warm and cold, non-perfused controls. The contralateral muscle served as the control. End-points were the percentage of muscle survival, as determined by a new grading system of muscle ischaemia, based on 3 light and 7 electron microscopic criteria. The overall percentage of muscle survival (combined light and electron microscopy scores) resulted in approximately 58% survival at 24 hours for the perfused muscle versus 31% for the cold stored muscle. The stored muscle had the same survival rate at 12 hours as did the perfused muscle at 24 hours. For all time periods beyond 4 to 8 hours, perfused muscle showed statistically improved survival rates compared to the stored muscle. Eight hours appears to be a crucial point beyond which survival in muscle deteriorates to a much greater degree without perfusion. Questions remain as to which method of preservation yields the best survival benefit and, as yet, there is no “ideal” perfusate. The future involves manipulating perfusion solutions and trying to arrest or reverse established warm ischaemia. Success of free tissue transfers and replantations of musclecontaining body parts may be enhanced. These techniques may also allow us to effectively store previously harvested flaps and eventually, to enter the realm of “banked” allograft tissue flaps.

<p>Cilj: Kod trećine bolesnika sa akutnim ST-eleviranim infarktom (STEMI) nakon primarne angioplastike (pPCI) razvije se postinfarktno remodelovanje leve komore (LK). Cilj istraživanja je nalaženje ranih prediktora post-infarktnog remodelovanja leve komore nakon akutnog STEMI i pPCI. Metodologija: Uključeno je 210 ispitanika sa prvim akutnim STEMI prednjeg zida, lečenih pPCI. Urađena je ehokardiografija u prva 24h, a zatim nakon 6 meseci, kada su ispitanici podeljeni u 2 grupe: ispitivanu sa remodelovanjem (n=55; 26%) i kontrolnu bez remodelovanja (n=155; 74%). Ispitanici su klinički praćeni godinu dana. Rezultati i dikusija: Multivarijantnom regresionom analizom, kao najsnažniji rani prediktori post-infarktnog remodelovanja izdvojili su se: postojanje &quot;no reflow&quot; fenomena nakon pPCI (OR=30.0 95% CI, p&lt;0.0001), pojava dijastolne disfunkcije u prva 24h (OR=27.7 95% CI, p&lt;0.0001), povećan dijametar leve pretkomore - LA (OR=5.0 95% CI, p=0,044) i srčana slabost na prijemu - Killip klasa 2-4 (OR=3.4 95% CI, p=0.003.). Univarijantnom regresionom analizom, snažni prediktori su neadekvatna rezolucija ST segmenta - STR (OR 2.0 95% CI, p=0.024) i zbirni indeks zidne pokretljivosti &ndash; WMSI &gt;2 (OR 21.6 95% CI, p&lt;0.0001). Totalno ishemijsko vreme nije imalo uticaja na post-infarktno remodelovanje (p=0.546). Tokom jednogodi&scaron;njeg praćenja ispitanici sa post-infarktnim remodelovanjem su imali značajno veću incidencu glavnih neželjenih kardiolo&scaron;kih događaja: rehospitalizacija (61.8% vs 22.6%; p&lt;0.0001) / najvi&scaron;e rehospitalizacija zbog srčane slabosti (40% vs 2.6%; p&lt;0.0001), sa mortalitetom 5.5%/; reinfarkta (20% vs 7.1%; p=0.007); rekoronarografija (45.5% vs 18.1%; p&lt;0.0001); revaskularizacija (30.9% vs 11%; p=0.001). Zaključak: Kod pacijenata sa akutnim STEMI prednjeg zida lečenih pPCI, pojava &quot;no reflow&quot; fenomena, dijastolne disfunkcije, povećana LA i srčana slabosti na prijemu su najjači rani nezavisni prediktivni faktori za nastanak post-infarktnog remodelovanja. Značajni prediktori su i neadekvatna STR i WMSI&gt;2. Pacijenti sa post-infarktnim remodelovanjem imaju veću incidencu glavnih neželjenih kardiolo&scaron;kih događaja i mortaliteta.</p> / <p>Objective: Patients with ST-elevated myocardial infarction (STEMI) treated by primary angioplasty (pPCI) will develop left ventricular (LV) remodeling in one third of the cases. The purpose of this study is to determine early predictors of LV remodeling after acute STEMI and pPCI. Methods: 210 patients with a first acute anterior STEMI treated by pPCI were included. All participants underwent echocardiography in the first 24hrs and again after 6 months, after which they were divided into two groups: remodeling (n=55; 26%) and nonremodeling (n=155; 74%). Results and discussion: The most powerful independent early predictors were: &quot;no reflow&quot; after pPCI (OR=30.0 95% CI, p&lt;0.0001), diastolic dysfunction in the first 24hrs (OR=27.7 95% CI, p&lt;0.0001), increased diameter of the left atrium - LA (OR=5.0 95% CI, p=0.044) and at admission Killip class 2-4 (OR=3.4 95% CI, p=0.003), by multivariant regression analysis. Also, strong predictors were incomplete ST-resolution - STR (OR 2.0 95% CI, p=0.024) and Wall motion score index - WMSI &gt;2 (OR 21.6 95% CI, p&lt;0.0001), by univariant regression analysis. Total ischaemic time had no influence on LV remodeling. The group with remodeling had more frequent major adverse cardiac events (MACE) during one year follow-up: re-hospitalisation (61.8% vs 22.6%; p&lt;0.0001) / mostly re-hospitalisation due to heart failure (40% vs 2.6%; p&lt;0.0001) and mortality 5.5%; reinfarction (20% vs 7.1%; p=0.007); recoronagraphy (45.5% vs 18.1%; p&lt;0.0001); revascularisation (30.9% vs 11%; p=0.001). Conclusion: For the patients with a first acute anterior STEMI, treated by pPCI, development of &quot;no reflow&quot; after pPCI, diastolic dysfunction, increased LA and heart failure on admission are the most powerful early independent predictors for LV remodeling. Incomplete STR and WMSI&gt;2 are strong predictors too. Remodeling patients will have a more frequent incidence of MACE and mortality.</p>